Radicicol derivatives, their preparation and their anti-tumor activity

ABSTRACT

Radicicol derivatives in which one or both hydroxy groups are acylated have valuable anti-tumor activity or may be used as chemical intermediates.

This application is a continuation of application Ser. No. 08/246,937filed May 20, 1994, now abandoned which is a continuation of applicationSer. No. 07/988,167 filed Dec. 9, 1992 (abandoned), which is acontinuation in part of application Ser. No. 07/711,217 filed Jun. 6,1991 (abandoned).

BACKGROUND OF THE INVENTION

The present invention relates to a series of new derivatives of thecompound "radicicol", which is also known by the name "monorden", andprovides methods and compositions using them as well as processes fortheir preparation.

Radicicol (Merck Index, 11th Edition, monograph No 6163, "Monorden") wasfirst isolated in 1953, and its structure was elucidated in 1964 byMirrington et al. [Tetrahedron Letters, 7, 365 (1964)], who alsodisclosed the diacetyl derivative of radicicol. At that time, it wasknown to have an activity which can be broadly described as "antibiotic"(as it is described in the Merck Index), although, in fact, its activityis strictly anti-fungal. It is also known to have a relatively strongtranquilizing activity without having any effect on the central nervoussystem. Subsequently, it was disclosed in U.S. Pat. No. 3,428,526 thatradicicol has a strong inhibitory effect in vitro on the growth of tumorcells of the mouse mastocytoma P-815. However, to date, no commercialuse for the compound has been found.

We have found that radicicol itself can exert little anti-tumor activityagainst various types of tumor in vivo, and have also surprisingly foundthat certain acylated derivatives of radicicol demonstrate a superioranti-tumor activity. It is believed that the relative inactivity in vivocompared to the good activity in vitro may be a result of an instabilityof the compound to a component of the mammalian metabolism. We have,however, found that acylated derivatives of radicicol have greaterstability in the mammalian body and can, therefore, be of practical usein the treatment of tumors.

BRIEF SUMMARY OF INVENTION

It is, therefore, an object of the present invention to provide as newcompositions of matter a series of novel acylated radicicol derivatives.

It is a further object of the present invention to provide suchcompounds which may demonstrate anti-tumor activity.

Other objects and advantages of the present invention will becomeapparent as the description proceeds.

The compounds of the present invention are those compounds of formula(I): ##STR1## in which: R¹ and R² are independently selected from thegroup consisting of hydrogen atoms and groups of formula R³ --CO--,where each of the symbols R³ is independently selected from the groupsconsisting of:

hydrogen atoms;

alkyl groups having from 1 to 50 carbon atoms;

substituted alkyl groups which have from 1 to 50 carbon atoms and whichare substituted by at least one substituent selected from the groupconsisting of substituents (a), defined below;

alkoxy groups which have from 1 to 20 carbon atoms and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of substituents (a), defined below;

alkenyl groups having from 2 to 30 carbon atoms and having at least onecarbon-carbon double bond;

substituted alkenyl groups which have from 2 to 30 carbon atoms, whichhave at least one carbon-carbon double bond and which are substituted byat least one substituent selected from the group consisting ofsubstituents (a), defined below;

alkenyloxy groups which have from 2 to 30 carbon atoms and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of substituents (a), defined below;

alkynyl groups having from 2 to 10 carbon atoms;

substituted alkynyl groups which have from 2 to 10 carbon atoms andwhich are substituted by at least one substituent selected from thegroup consisting of substituents (a), defined below;

aryl groups which have from 6 to 14 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

aryloxy groups which have from 6 to 14 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

heterocyclic groups which have 5 or 6 ring atoms, of which from 1 to 3are selected from the group consisting of nitrogen, oxygen and sulfurhetero-atoms, said heterocyclic group being unsubstituted or beingsubstituted by at least one substituent selected from the groupconsisting of substituents (c), defined below;

heterocyclic groups which have 5 or 6 ring atoms, of which from 1 to 3are selected from the group consisting of nitrogen, oxygen and sulfurhetero-atoms, and which are fused to an aryl group, said heterocyclicgroup or aryl group being unsubstituted or being substituted by at leastone substituent selected from the group consisting of substituents (c),defined below;

cycloalkyl groups which have from 3 to 8 carbon atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (c), defined below;

cycloalkenyl groups which have from 5 to 8 carbon atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (c), defined below;

cycloalkyl groups which have from 3 to 8 carbon atoms and are fused toan aryl group which has from 6 to 10 ring carbon atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (c), defined below;

substituents (a)

hydroxy groups;

alkoxy groups which have from 1 to 20 carbon atoms and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of alkoxy groups having from 1 to 4 carbonatoms and alkylthio groups having from 1 to 4 carbon atoms;

aryl groups which have from 6 to 14 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

aryloxy groups which have from 6 to 10 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

aliphatic carboxylic acyloxy groups having from 1 to 20 carbon atoms;

aliphatic carboxylic acylthio groups having from 1 to 20 carbon atoms;

aromatic carboxylic acyloxy groups in which the aryl part has from 6 to10 ring carbon atoms and is unsubstituted or is substituted by at leastone substituent selected from the group consisting of substituents (b),defined below;

groups of formula --NR⁴ R⁵, --CONHR⁴ R⁵ and --OCONHR⁴ R⁵, where R⁴ andR⁵ are independently selected from the group consisting of:

hydrogen atoms; alkyl groups having from 1 to 4 carbon atoms; aliphaticcarboxylic acyloxy groups having from 1 to 20 carbon atoms and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of substituents (a) other than said groups offormula --NR⁴ R⁵, --CONHR⁴ R⁵ and --OCONHR⁴ R⁵ ;

aromatic carboxylic acyloxy groups in which the aryl part has from 6 to10 ring carbon atoms and is unsubstituted or is substituted by at leastone substituent selected from the group consisting of substituents (b),defined below; alkoxycarbonyl groups in which the alkoxy part has from 1to 20 carbon atoms and which are unsubstituted or are substituted by atleast one substituent selected from the group consisting of substituents(a) other than said groups of formula --NR⁴ R⁵, --CONHR⁴ R⁵ and--OCONHR⁴ R⁵ ; alkylthio groups which have from 1 to 4 carbon atoms andwhich unsubstituted or are substituted by at least one substituentselected from the group consisting of substituents (a) other than saidalkylthio groups;

and aryloxycarbonyl groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined below;

carboxy groups;

alkoxycarbonyl groups in which the alkoxy part has from 1 to 20 carbonatoms;

aryloxycarbonyl groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined below;

mercapto groups;

alkylthio groups having from 1 to 20 carbon atoms;

arylthio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

aralkylthio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined below,and the alkyl part has from 1 to 4 carbon atoms;

aralkyldithio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined below,and the alkyl part has from 1 to 4 carbon atoms;

aryldithio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

alkyldithio groups which have from 1 to 20 carbon atoms;

alkylsulfinyl groups which have from 1 to 20 carbon atoms;

arylsulfinyl groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

alkylsulfonyl groups which have from 1 to 20 carbon atoms;

arylsulfonyl groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined below;

cyano groups;

aliphatic carboxylic acyl groups having from 1 to 20 carbon atoms;

aromatic carboxylic acyl groups in which the aryl part has from 6 to 10ring carbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined below;

cycloalkyl groups having from 3 to 8 ring atoms, and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of alkyl groups having from 1 to 4 carbonatoms;

cycloalkenyl groups having from 5 to 8 ring atoms, and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of alkyl groups having from 1 to 4 carbonatoms;

tri-substituted silyl groups in which the substituents are independentlyselected from the group consisting of alkyl groups having from 1 to 6carbon atoms and aryl groups having from 6 to 10 carbon atoms;

heterocyclic groups which have 5 or 6 ring atoms, of which from 1 to 3are selected from the group consisting of nitrogen, oxygen and sulfurhetero-atoms, said heterocyclic group being unsubstituted or beingsubstituted by at least one substituent selected from the groupconsisting of substituents (c), defined below; and

halogen atoms;

substituents (b)

alkyl groups having from 1 to 8 carbon atoms;

hydroxy groups;

alkoxy groups having from 1 to 20 carbon atoms;

aryl groups which have from 6 to 10 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an aryl group, it is notsubstituted by a further group which is or contains an aryl group;

aryloxy groups which have from 6 to 10 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an aryloxy group, it is notsubstituted by a further group which is or contains an aryl group;aliphatic carboxylic acyloxy groups having from 1 to 20 carbon atoms;

aromatic carboxylic acyloxy groups in which the aryl part has from 6 to10 ring carbon atoms and is unsubstituted or is substituted by at leastone substituent selected from the group consisting of substituents (b),defined here, provided that, where substituent (b) is an aromaticcarboxylic acyloxy group, it is not substituted by a further group whichis or contains an aryl group;

groups of formula --NR⁴ R⁵, --CONHR⁴ R⁵ and --OCONHR⁴ R⁵, where R⁴ andR⁵ are as defined above;

carboxy groups;

alkoxycarbonyl groups in which the alkoxy part has from 1 to 20 carbonatoms;

aryloxycarbonyl groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined here, provided that, where substituent (b) is an aryloxycarbonylgroup, it is not substituted by a further group which is or contains anaryl group;

mercapto groups;

alkylthio groups having from 1 to 20 carbon atoms;

arylthio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an arylthio group, it is notsubstituted by a further group which is or contains an aryl group;

aralkylthio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an aralkylthio group, it is notsubstituted by a further group which is or contains an aryl group, andthe alkyl part has from 1 to 4 carbon atoms;

aralkyldithio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an aralkyldithio group, it isnot substituted by a further group which is or contains an aryl group,and the alkyl part has from 1 to 4 carbon atoms;

aryldithio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an aryldithio group, it is notsubstituted by a further group which is or contains an aryl group;

alkyldithio groups which have from 1 to 20 carbon atoms;

alkylsulfinyl groups which have from 1 to 20 carbon atoms;

arylsulfinyl groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an arylsulfinyl group, it is notsubstituted by a further group which is or contains an aryl group;

alkylsulfonyl groups which have from 1 to 20 carbon atoms;

arylsulfonyl groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined here,provided that, where substituent (b) is an arylsulfinyl group, it is notsubstituted by a further group which is or contains an aryl group, andthe alkyl part has from 1 to 4 carbon atoms;

cyano groups;

aliphatic carboxylic acyl groups having from 1 to 20 carbon atoms;

aromatic carboxylic acyl groups in which the aryl part has from 6 to 10ring carbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined here, provided that, where substituent (b) is an aromaticcarboxylic acyl group, it is not substituted by a further group which isor contains an aryl group;

heterocyclic groups which have 5 or 6 ring atoms, of which from 1 to 3are selected from the group consisting of nitrogen, oxygen and sulfurhetero-atoms, said heterocyclic group being unsubstituted or beingsubstituted by at least one substituent selected from the groupconsisting of substituents (c), defined below; and

halogen atoms;

substituents (c)

oxygen atoms (to form an oxo group);

alkyl groups having from 1 to 8 carbon atoms;

hydroxy groups;

alkoxy groups having from 1 to 20 carbon atoms;

aryl groups which have from 6 to 10 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined above;

aryloxy groups which have from 6 to 10 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined above;

aliphatic carboxylic acyloxy groups having from 1 to 20 carbon atoms;

aromatic carboxylic acyloxy groups in which the aryl part has from 6 to10 ring carbon atoms and is unsubstituted or is substituted by at leastone substituent selected from the group consisting of substituents (b),defined above;

groups of formula --NR⁴ R⁵, --CONHR⁴ R⁵ and --OCONHR⁴ R⁵, where R⁴ andR⁵ are as defined above;

carboxy groups;

alkoxycarbonyl groups in which the alkoxy part has from 1 to 20 carbonatoms;

aryloxycarbonyl groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined above;

mercapto groups;

alkylthio groups having from 1 to 20 carbon atoms;

arylthio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined above;

aralkylthio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined above,and the alkyl part has from 1 to 4 carbon atoms;

aralkyldithio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined above,and the alkyl part has from 1 to 4 carbon atoms;

aryldithio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined above;

alkyldithio groups which have from 1 to 20 carbon atoms;

alkylsulfinyl groups which have from 1 to 20 carbon atoms;

arylsulfinyl groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined above;

alkylsulfonyl groups which have from 1 to 20 carbon atoms;

arylsulfonyl groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined above,and the alkyl part has from 1 to 4 carbon atoms;

cyano groups;

aliphatic carboxylic acyl groups having from 1 to 20 carbon atoms;

aromatic carboxylic acyl groups in which the aryl part has from 6 to 10ring carbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined above;

heterocyclic groups which have 5 or 6 ring atoms, of which from 1 to 3are selected from the group consisting of nitrogen, oxygen and sulfurhetero-atoms, said heterocyclic group being unsubstituted or beingsubstituted by at least one substituent selected from the groupconsisting of substituents (c), defined here, provided that, wheresubstituent (c) is a heterocyclic group, it is not substituted by afurther heterocyclic group; and

halogen atoms;

PROVIDED THAT R¹ and R² do not both represent hydrogen atoms AND THAT R¹and R² do not both represent acetyl groups;

and pharmaceutically acceptable salts thereof.

The invention also provides a pharmaceutical composition for thetreatment or prophylaxis of tumors, which comprises an effective amountof an active compound in admixture with a pharmaceutically acceptablecarrier or diluent, wherein said active compound is selected from thegroup consisting of compounds of formula (I) and salts thereof, asdefined above.

The invention also provides a method for the treatment or prophylaxis oftumors, which comprises administering to an animal, e.g. a mammal, whichmay be human, an effective amount of an active compound, wherein saidactive compound is selected from the group consisting of compounds offormula (I) and salts thereof, as defined above.

The invention also provides various processes for preparing thecompounds of the present invention, which are described in greaterdetail hereafter.

DETAILED DESCRIPTION OF INVENTION

In the compounds of the present invention, where R³ represents an alkylgroup, this has from 1 to 50 carbon atoms, and may be a straight orbranched chain group. Examples of such groups include the methyl, ethyl,propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl,3-methylbutyl, 2,2-dimethylpropyl, 1,1-dimethylpropyl, hexyl,1-methylpentyl, 4-methylpentyl, heptyl, 1-methylhexyl, 2-methylhexyl,5-methylhexyl, 3-ethylpentyl, octyl, 2-methylheptyl, 6-methylheptyl,2-ethylhexyl, 2-ethyl-3-methylpentyl, 3-ethyl-2-methylpentyl, nonyl,2-methyloctyl, 7-methyloctyl, 4-ethylheptyl, 3-ethyl-2-methylhexyl,2-ethyl-1-methylhexyl, decyl, 2-methylnonyl, 8-methylnonyl,5-ethyloctyl, 3-ethyl-2-methylheptyl, 3,3-diethylhexyl, undecyl,2-methyldecyl, 9-methyldecyl, 4-ethylnonyl, 3,5-dimethylnonyl,3-propyloctyl, 5-ethyl-4-methyloctyl, 1-pentylhexyl, dodecyl,1-methylundecyl, 10-methylundecyl, 3-ethyldecyl, 5-propylnonyl,3,5-diethyloctyl, tridecyl, 11-methyldodecyl, 7-ethylundecyl,4-propyldecyl, 5-ethyl-3-methyldecyl, 3-pentyloctyl, tetradecyl,12-methyltridecyl, 8-ethyldodecyl, 6-propylundecyl, 4-butyldecyl,2-pentylnonyl, pentadecyl, 13-methyltetradecyl, 10-ethyltridecyl,7-propyldodecyl, 5-ethyl-3-methyldodecyl, 4-pentyldecyl, 1-hexylnonyl,hexadecyl, 14-methylpentadecyl, 6-ethyltetradecyl, 4-propyltridecyl,2-butyldodecyl, heptadecyl, 15-methylhexadecyl, 7-ethylpentadecyl,3-propyltetradecyl, 5-pentyldodecyl, octadecyl, 16-methylheptadecyl,5-propylpentadecyl, nonadecyl, 17-methyloctadecyl, 4-ethylheptadecyl,icosyl, 18-methylnonadecyl, 3-ethyloctadecyl, henicosyl, docosinyl,tricosinyl, tetracosinyl and pentacosinyl groups. Certain of theacylated radicicol derivatives of the present invention may not beeasily soluble in the most common physiologically acceptable solvents,and in such cases (which most notably include the derivatives of thelonger chain aliphatic acids), a special solvent system may be employedto solubilize the compound, as is well known in the art and can readilybe determined by the man skilled in the art. However, to avoid the needfor this, shorter chain alkyl groups among those represented by R³ arepreferred, for example those alkyl groups having from 1 to 25 carbonatoms, more preferably from 8 to 20 carbon atoms, and most preferablyfrom 12 to 17 carbon atoms (i.e. the alkanoyl group represented by R¹ orR² would have from 2 to 26, more preferably from 9 to 21 and mostpreferably from 13 to 18, carbon atoms).

Where R³ represents a substituted alkyl group, this may be any of thosegroups listed above, which is substituted by at least one ofsubstituents (a), defined above and exemplified below.

In relation to these, and all substituted groups where a specific numberof substituents is not given, there is no particular restriction on thenumber of such groups, except as may be required by the number ofsubstitutable atoms, or possibly by steric constraints. In general,however, we prefer (provided there are sufficient subtitutable atoms)from 1 to 5 substituents, more preferably from 1 to 3 substituents.

Among substituents (a), are included aryl groups, which may be asdefined above and exemplified below. Such substituted groups are aralkylgroups, and these preferably have from 1 to 4 carbon atoms in the alkylpart and from 1 to 10 carbon atoms in the aryl part. The aryl part maybe substituted or unsubstituted. Examples of such aralkyl groups includethe benzyl, phenethyl, 1-phenylethyl, 1-, 2- and 3-phenylpropyl, 1-, 2-,3-, 4- and 5-phenylpentyl and the 1- and 2-naphthylmethyl groups.

Where R³ represents an alkoxy group, this has from 1 to 20 carbon atoms,and may be a straight or branched chain group. Examples of such groupsinclude the methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,sec-butoxy, t-butoxy, pentoxy, 3-methylbutoxy, 2,2-dimethylpropoxy,1,1-dimethylpropoxy, hexyloxy, 1-methylpentyloxy, 4-methylpentyloxy,heptyloxy, 1-methylhexyloxy, 2-methylhexyloxy, 5-methylhexyloxy,3-ethylpentyloxy, octyloxy, 2-methylheptyloxy, 6-methylheptyloxy,2-ethylhexyloxy, 2-ethyl-3-methylpentyloxy, 3-ethyl-2-methylpentyloxy,nonyloxy, 2-methyloctyloxy, 7-methyloctyloxy, 4-ethylheptyloxy,3-ethyl-2-methylhexyloxy, 2-ethyl-1-methylhexyloxy, decyloxy,2-methylnonyloxy, 8-methylnonyloxy, 5-ethyloctyloxy,3-ethyl-2-methylheptyloxy, 3,3-diethylhexyloxy, undecyloxy,2-methyldecyloxy, 9-methyldecyloxy, 4-ethylnonyloxy,3,5-dimethylnonyloxy, 3-propyloctyloxy, 5-ethyl-4-methyloctyloxy,1-pentylhexyloxy, dodecyloxy, 1-methylundecyloxy, 10-methylundecyloxy,3-ethyldecyloxy, 5-propylnonyloxy, 3,5-diethyloctyloxy, tridecyloxy,11-methyldodecyloxy, 7-ethylundecyloxy, 4-propyldecyloxy,5-ethyl-3-methyldecyloxy, 3-pentyloctyloxy, tetradecyloxy,12-methyltridecyloxy, 8-ethyldodecyloxy, 6-propylundecyloxy,4-butyldecyloxy, 2-pentylnonyloxy, pentadecyloxy,13-methyltetradecyloxy, 10-ethyltridecyloxy, 7-propyldodecyloxy,5-ethyl-3-methyldodecyloxy, 4-pentyldecyloxy, 1-hexylnonyloxy,hexadecyloxy, 14-methylpentadecyloxy, 6-ethyltetradecyloxy,4-propyltridecyloxy, 2-butyldodecyloxy, heptadecyloxy,15-methylhexadecyloxy, 7-ethylpentadecyloxy, 3-propyltetradecyloxy,5-pentyldodecyloxy, octadecyloxy, 16-methylheptadecyloxy,5-propylpentadecyloxy, nonadecyloxy, 17-methyloctadecyloxy,4-ethylheptadecyloxy, icosyloxy and 18-methylnonadecyloxy,3-ethyloctadecyloxy groups.

Where R³ represents a substituted alkoxy group, this may be any of thosegroups listed above, which is substituted by at least one ofsubstituents (a), defined above and exemplified below.

Where R³ represents an alkenyl group, this has from 2 to 30 carbonatoms, and may be a straight or branched chain group. It may have 1 ormore, preferably from 1 to 4, double bonds. Examples of such groupsinclude the vinyl, allyl, 1-propenyl, isopropenyl, 2-methyl-1-propenyl,1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl,4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,1-heptenyl, 2-heptenyl, 3-heptenyl, 1-octenyl, 8-nonenyl, 1-nonenyl,1-decenyl, 9-decenyl, 8-tridecenyl, cis-8-pentadecenyl,trans-8-pentadecenyl, 8-heptadecenyl, 8-heptadecenyl,8,11-heptadecadienyl, 8,11,14-heptadecatrienyl,4,7,11,14-nonadecatetraenyl and2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,7-nonatetraen-1-ylgroups.

Where R³ represents a substituted alkenyl group, this may be any ofthose groups listed above, which is substituted by at least one ofsubstituents (a), defined above and exemplified below.

Where R³ represents an alkynyl group, this has from 2 to 10 carbonatoms, and may be a straight or branched chain group. Examples of suchgroups include the ethynyl, 1-propynyl, propargyl, 1-heptynyl, 1-octynyland 1-decynyl groups.

Where R³ represents a substituted alkynyl group, this may be any ofthose groups listed above, which is substituted by at least one ofsubstituents (a), defined above and exemplified below.

Where R³ represents an aryl group, this has from 6 to 14 ring atoms, ina single or multiple rings, and examples include the phenyl, 1-naphthyl,2-naphthyl, fluorenyl, 1-anthryl and 1-phenanthryl groups. Such groupsmay be substituted or unsubstituted, and, if substituted, thesubstituents are selected from the group consisting of substituents (a),defined above and exemplified below.

Where R³ represents an aryloxy group, this has from 6 to 14 ring atoms,in a single or multiple rings, and examples include the phenoxy,1-naphthyloxy, 2-naphthyloxy, fluorenyloxy, 1-anthryloxy and1-phenanthryloxy groups. Such groups may be substituted orunsubstituted, and, if substituted, the substituents are selected fromthe group consisting of substituents (a), defined above and exemplifiedbelow.

Where R³ represents a heterocyclic group, this has 5 or 6 ring atoms. Ofthese atoms, from 1 to 3 are hetero-atoms selected from the groupconsisting of nitrogen, oxygen and sulfur hetero-atoms. Where there are3 hetero-atoms, we prefer that at least one (more preferably 2) shouldbe a nitrogen atom and one or two should be nitrogen, oxygen or sulfuratoms (and, where there are two, they may be the same or different).Where there are two hetero-atoms, these may be the same or different andthey are selected from nitrogen, oxygen and sulfur atoms; however, morepreferably one is a nitrogen atom and the other is a nitrogen, oxygen orsulfur atom. Such groups may be unsubstituted or they may be substitutedby at least one (preferably from 1 to 3) of substituents (c), definedand exemplified above. Examples of such unsubstituted groups include thefuryl, thienyl, pyrrolyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl,isoxazolyl, imidazolyl, pyrazolyl, pyranyl, pyrazinyl, pyridazinyl,pyrimidinyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl,thiazolidinyl, thiazolinyl, isothiazolinyl, imidazolidinyl,imidazolinyl, oxazolinyl, isoxazolinyl, oxazolidinyl, pyrazolidinyl,piperazinyl, dioxopiperazinyl, tetrahydropyrimidinyl,dihydropyridazinyl, morpholinyl, thiomorpholinyl, pyrrolidonyl,piperidonyl, pyridonyl, 2H-pyrrolyl, furazanyl and pyrazolinyl groups,especially the furyl, pyrrolyl, pyridyl, thiazolyl, isothiazolyl,oxazolyl, isoxazolyl, imidazolyl, pyridazinyl, pyrrolidinyl,thiazolinyl, isothiazolinyl, imidazolyl, piperazinyl, dioxopiperazinyl,morpholinyl, pyrrolidonyl and piperidonyl groups. Such groups may beunsubstituted or they may have at least one substituent selected fromthe group consisting of substituents (c), defined above and exemplifiedbelow.

Where R³ represents a cycloalkyl group, this has from 3 to 8 carbonatoms and may be unsubstituted or substituted. If it is substituted, ithas at least one substituent selected from the group consisting ofsubstituents (c), defined above and exemplified below. Examples of suchgroups include the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cyclopentyl and cyclooctyl groups and substituted analogs thereof.

Where R³ represents a cycloalkenyl group, this has from 5 to 8 carbonatoms and may be unsubstituted or substituted. If it is substituted, ithas at least one substituent selected from the group consisting ofsubstituents (c), defined above and exemplified below. It has one ormore, preferably 1 or 2, more preferably 1, carbon-carbon double bond.Examples of such groups include the 1-cyclopenten-1-yl,2-cyclopenten-1-yl, 1-cyclohexen-1-yl, 2-cyclohexen-1-yl,3-cyclohexen-1-yl, 1-cylohepten-1-yl, 2-cyclohepten-1-yl,1-cycloocten-1-yl and 3-cycloocten-1-yl groups and substituted analogsthereof.

Where R³ represents a cycloalkyl group fused to an aryl group, thecycloalkyl part has from 3 to 8 carbon atoms and the aryl part has from6 to 10 carbon atoms (and is preferably a benzene ring). The group maybe unsubstituted or substituted. If it is substituted, it has at leastone substituent selected from the group consisting of substituents (c),defined above and exemplified below. Examples of such groups include theindanyl and tetrahydronaphthyl groups.

Examples of groups and atoms which may be included in substituents (a)include:

1. hydroxy groups;

2. alkoxy groups which have from 1 to 20 carbon atoms and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of alkoxy groups having from 1 to 4 carbonatoms, such as the methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, sec-butoxy, t-butoxy, pentyloxy, methoxymethoxy,1-methoxyethoxy, 2-methoxyethoxy, butoxymethoxy, 2-butoxyethoxy,3-ethoxypropoxy, 3-methylbutoxy, 2,2-dimethylpropoxy,1,1-dimethylpropoxy, hexyloxy, 1-methylpentyloxy, 4-methylpentyloxy,heptyloxy, 1-methylhexyloxy, 2-methylhexyloxy, 5-methylhexyloxy,3-ethylpentyloxy, octyloxy, 2-methylheptyloxy, 6-methylheptyloxy,2-ethylhexyloxy, 2-ethyl-3-methylpentyloxy, 3-ethyl-2-methylpentyloxy,nonyloxy, 2-methyloctyloxy, 7-methyloctyloxy, 4-ethylheptyloxy,3-ethyl-2-methylhexyloxy, 2-ethyl-1-methylhexyloxy, decyloxy,2-methylnonyloxy, 8-methylnonyloxy, 5-ethyloctyloxy,3-ethyl-2-methylheptyloxy, 3,3-diethylhexyloxy, undecyloxy,2-methyldecyloxy, 9-methyldecyloxy, 4-ethylnonyloxy,3,5-dimethylnonyloxy, 3-propyloctyloxy, 5-ethyl-4-methyloctyloxy,1-pentylhexyloxy, dodecyloxy, 1-methylundecyloxy, 10-methylundecyloxy,3-ethyldecyloxy, 5-propylnonyloxy, 3,5-diethyloctyloxy, tridecyloxy,11-methyldodecyloxy, 7-ethylundecyloxy, 4-propyldecyloxy,5-ethyl-3-methyldecyloxy, 3-pentyloctyloxy, tetradecyloxy,12-methyltridecyloxy, 8-ethyldodecyloxy, 6-propylundecyloxy,4-butyldecyloxy, 2-pentylnonyloxy, pentadecyloxy,13-methyltetradecyloxy, 10-ethyltridecyloxy, 7-propyldodecyloxy,5-ethyl-3-methyldodecyloxy, 4-pentyldecyloxy, 1-hexylnonyloxy,hexadecyloxy, 14-methylpentadecyloxy, 6-ethyltetradecyloxy,4-propyltridecyloxy, 2-butyldodecyloxy, heptadecyloxy,15-methylhexadecyloxy, 7-ethylpentadecyloxy, 3-propyltetradecyloxy,5-pentyldodecyloxy, octadecyloxy, 16-methylheptadecyloxy,5-propylpentadecyloxy, nonadecyloxy, 17-methyloctadecyloxy,4-ethylheptadecyloxy, icosyloxy and 18-methylnonadecyloxy,3-ethyloctadecyloxy groups;

3. aryl groups which have from 6 to 14 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined aboveand exemplified below, such as the phenyl, 1-naphthyl, 2-naphthyl,fluorenyl, 1-anthryl and 1-phenanthryl groups;

4. aryloxy groups which have from 6 to 10 ring atoms and which areunsubstituted or which are substituted by at least one substituentselected from the group consisting of substituents (b), defined aboveand exemplified below, such as the phenoxy, 1-naphthyloxy,2-naphthyloxy, fluorenyloxy, 1-anthryloxy and 1-phenanthryloxy groups;

5. aliphatic carboxylic acyloxy groups having from 1 to 22, preferablyfrom 1 to 20, carbon atoms, such as the formyloxy, acetoxy,propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy,pivaloyloxy, hexanoyloxy, 2-methylpentanoyloxy, 2-ethylbutyryloxy,heptanoyloxy, 2-methylhexanoyloxy, 4-methylhexanoyloxy,2-ethylpentanoyloxy, octanoyloxy, 2-methylheptanoyloxy,4-methylheptanoyloxy, 2-ethylhexanoyloxy, nonanoyloxy,2-methyloctanoyloxy, 5-methyloctanoyloxy, 2-ethylheptanoyloxy,nonylcarbonyloxy, decylcarbonyloxy, 3-methylnonylcarbonyloxy,8-methylnonylcarbonyloxy, 3-ethyloctylcarbonyloxy,3,7-dimethyloctylcarbonyloxy, undecylcarbonyloxy, dodecylcarbonyloxy,tridecylcarbonyloxy, tetradecylcarbonyloxy, pentadecylcarbonyloxy,hexadecylcarbonyloxy, 1-methylpentadecylcarbonyloxy,14-methylpentadecylcarbonyloxy, 13,13-dimethyltetradecylcarbonyloxy,heptadecylcarbonyloxy, 15-methylhexadecylcarbonyloxy,octadecylcarbonyloxy, 1-methylheptadecylcarbonyloxy,nonadecylcarbonyloxy, icosylcarbonyloxy and henicosylcarbonyloxy groups;

6. aliphatic carboxylic acylthio groups having from 1 to 22, preferablyfrom 1 to 20, carbon atoms, such as the formylthio, acetylthio,propionylthio, butyrylthio, isobutyrylthio, valerylthio, isovalerylthio,pivaloylthio, hexanoylthio, 2-methylpentanoylthio, 2-ethylbutyrylthio,heptanoylthio, 2-methylhexanoylthio, 4-methylhexanoylthio,2-ethylpentanoylthio, octanoylthio, 2-methylheptanoylthio,4-methylheptanoylthio, 2-ethylhexanoylthio, nonanoylthio,2-methyloctanoylthio, 5-methyloctanoylthio, 2-ethylheptanoylthio,nonylcarbonylthio, decylcarbonylthio, 3-methylnonylcarbonylthio,8-methylnonylcarbonylthio, 3-ethyloctylcarbonylthio,3,7-dimethyloctylcarbonylthio, undecylcarbonylthio, dodecylcarbonylthio,tridecylcarbonylthio, tetradecylcarbonylthio, pentadecylcarbonylthio,hexadecylcarbonylthio, 1-methylpentadecylcarbonylthio,14-methylpentadecylcarbonylthio, 13,13-dimethyltetradecylcarbonylthio,heptadecylcarbonylthio, 15-methylhexadecylcarbonylthio,octadecylcarbonylthio, 1-methylheptadecylcarbonylthio,nonadecylcarbonylthio, icosylcarbonylthio and henicosylcarbonylthiogroups; such groups may be substituted or unsubstituted, and, ifsubstituted, the substituents are selected from the group consisting ofsubstituents (a), provided that any such substituent is not furthersubstituted by a group which is or contains such an aliphatic carboxylicacyl group;

7. aromatic carboxylic acyloxy groups in which the aryl part has from 6to 10 ring carbon atoms and is unsubstituted or is substituted by atleast one substituent selected from the group consisting of substituents(b), defined above and exemplified below; examples include the benzoyland naphthoyl groups and substituted analogs thereof;

8. groups of formula --NR⁴ R⁵, --CONHR⁴ R⁵ and --OCONHR⁴ R⁵, where R⁴and R⁵ are independently selected from the group consisting of:

hydrogen atoms; alkyl groups having from 1 to 4 carbon atoms (e.g. themethyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and t-butylgroups); aliphatic carboxylic acyloxy groups having from 1 to 20 carbonatoms and which are unsubstituted or are substituted by at least onesubstituent selected from the group consisting of substituents (a) otherthan said groups of formula --NR⁴ R⁵, --CONHR⁴ R⁵ and --OCONHR⁴ R⁵ (e.g.as exemplified above); aromatic carboxylic acyloxy groups in which thearyl part has from 6 to 10 ring carbon atoms and is unsubstituted or issubstituted by at least one substituent selected from the groupconsisting of substituents (b), defined above and exemplified below(e.g. as exemplified above); alkoxycarbonyl groups in which the alkoxypart has from 1 to 20 carbon atoms and which are unsubstituted or aresubstituted by at least one substituent selected from the groupconsisting of substituents (a) other than said groups of formula --NR⁴R⁵, --CONHR⁴ R⁵ and --OCONHR⁴ R⁵ (e.g. those in which the alkoxy part isas exemplified above); alkylthio groups which have from 1 to 4 carbonatoms and which are unsubstituted or are substituted by at least onesubstituent selected from the group consisting of substituents (a) otherthan said alkylthio groups (e.g. the methylthio, ethylthio, propylthio,isopropylthio, butylthio, isobutylthio, sec-butylthio and t-butylthiogroups); and aryloxycarbonyl groups in which the aryl part has from 6 to10 ring carbon atoms and is unsubstituted or is substituted by at leastone substituent selected from the group consisting of substituents (b),defined below (e.g. the benzoyl and naphthoyl groups and substitutedanalogs thereof);

9. carboxy groups;

10. alkoxycarbonyl groups in which the alkoxy part has from 1 to 20carbon atoms, such as those groups in which the alkoxy part is asexemplified above;

11. aryloxycarbonyl groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined below, such as those groups in which the aryloxy part is asexemplified above;

12. mercapto groups;

13. alkylthio groups having from 1 to 20 carbon atoms, such as themethylthio, ethylthio, propylthio, isopropylthio, butylthio,isobutylthio, sec-butylthio, t-butylthio, pentylthio, 3-methylbutylthio,2,2-dimethylpropylthio, 1,1-dimethylpropylthio, hexylthio,1-methylpentylthio, 4-methylpentylthio, heptylthio, 1-methylhexylthio,2-methylhexylthio, 5-methylhexylthio, 3-ethylpentylthio, octylthio,2-methylheptylthio, 6-methylheptylthio, 2-ethylhexylthio,2-ethyl-3-methylpentylthio, 3-ethyl-2-methylpentylthio, nonylthio,2-methyloctylthio, 7-methyloctylthio, 4-ethylheptylthio,3-ethyl-2-methylhexylthio, 2-ethyl-1-methylhexylthio, decylthio,2-methylnonylthio, 8-methylnonylthio, 5-ethyloctylthio,3-ethyl-2-methylheptylthio, 3,3-diethylhexylthio, undecylthio,2-methyldecylthio, 9-methyldecylylthio, 4-ethylnonylthio,3,5-dimethylnonylthio, 3-propyloctylthio, 5-ethyl-4-methyloctylthio,1-pentylhexylthio, dodecylthio, 1-methylundecylthio,10-methylundecylthio, 3-ethyldecylthio, 5-propylnonylthio,3,5-diethyloctylthio, tridecylthio, 11-methyldodecylthio,7-ethylundecylthio, 4-propyldecylthio, 5-ethyl-3-methyldecylthio,3-pentyloctylthio, tetradecylthio, 12-methyltridecylthio,8-ethyldodecylthio, 6-propylundecylthio, 4-butyldecylthio,2-pentylnonylthio, pentadecylthio, 13-methyltetradecylthio,10-ethyltridecylthio, 7-propyldodecylthio, 5-ethyl-3-methyldodecylthio,4-pentyldecylthio, 1-hexylnonylthio, hexadecylthio,14-methylpentadecylthio, 6-ethyltetradecylthio, 4-propyltridecylthio,2-butyldodecylthio, heptadecylthio, 15-methylhexadecylthio,7-ethylpentadecylthio, 3-propyltetradecylthio, 5-pentyldodecylthio,octadecylthio, 16-methylheptadecylthio, 5-propylpentadecylthio,nonadecylthio, 17-methyloctadecylthio, 4-ethylheptadecylthio,icosylthio, 18-methylnonadecylthio and 3-ethyloctadecylthio groups;

14. arylthio groups in which the aryl part has from 6 to 10 ring carbonatoms and is unsubstituted or is substituted by at least one substituentselected from the group consisting of substituents (b), defined aboveand exemplified below (such as the phenylthio and naphthylthio groupsand substituted analogs thereof);

15. aralkylthio groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined below, and the alkyl part has from 1 to 4 carbon atoms, such asthe benzylthio, phenethylthio, 1-phenylethylthio, 1-, 2- and3-phenylpropylthio, 1-, 2-, 3-, 4- and 5-phenylpentylthio and the 1- and2-naphthylmethylthio groups;

16. aralkyldithio groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined below, and the alkyl part has from 1 to 4 carbon atoms, such asthe benzyldithio, phenethyldithio, 1-phenylethyldithio, 1-, 2- and3-phenylpropyldithio, 1-, 2-, 3-, 4- and 5-phenylpentyldithio and the 1-and 2-naphthylmethyldithio groups;

17. aryldithio groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined above and exemplified below (such as the phenyldithio andnaphthyldithio groups and substituted analogs thereof);

18. alkyldithio groups which have from 1 to 20 carbon atoms, such as thedithio analogs of the alkylthio groups exemplified above;

19. alkylsulfinyl groups which have from 1 to 20 carbon atoms, such asthe sulfinyl analogs of the alkylthio groups exemplified above;

20. arylsulfinyl groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined above and exemplified below, such as the sulfinyl analogs of thearylthio groups exemplified above;

21. alkylsulfonyl groups which have from 1 to 20 carbon atoms, such asthe sulfonyl analogs of the alkylthio groups exemplified above;

22. arylsulfonyl groups in which the aryl part has from 6 to 10 ringcarbon atoms and is unsubstituted or is substituted by at least onesubstituent selected from the group consisting of substituents (b),defined below, such as the sulfonyl analogs of the arylthio groupsexemplified above;

23. cyano groups;

24. aliphatic carboxylic acyl groups having from 1 to 20 carbon atoms,such as the formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl,isovaleryl, pivaloyl, hexanoyl, 2-methylpentanoyl, 2-ethylbutyryl,heptanoyl, 2-methylhexanoyl, 4-methylhexanoyl, 2-ethylpentanoyl,octanoyl, 2-methylheptanoyl, 4-methylheptanoyl, 2-ethylhexanoyl,nonanoyl, 2-methyloctanoyl, 5-methyloctanoyl, 2-ethylheptanoyl,nonylcarbonyl, decylcarbonyl, 3-methylnonylcarbonyl,8-methylnonylcarbonyl, 3-ethyloctylcarbonyl, 3,7-dimethyloctylcarbonyl,undecylcarbonyl, dodecylcarbonyl, tridecylcarbonyl, tetradecylcarbonyl,pentadecylcarbonyl, hexadecylcarbonyl, 1-methylpentadecylcarbonyl,14-methylpentadecylcarbonyl, 13,13-dimethyltetradecylcarbonyl,heptadecylcarbonyl, 15-methylhexadecylcarbonyl, octadecylcarbonyl,1-methylheptadecylcarbonyl, nonadecylcarbonyl, icosylcarbonyl andhenicosylcarbonyl groups;

25. aromatic carboxylic acyl groups in which the aryl part has from 6 to10 ring carbon atoms and is unsubstituted or is substituted by at leastone substituent selected from the group consisting of substituents (b),defined above and exemplified below, such as the benzoyl and naphthoylgroups and substituted analogs thereof;

26. cycloalkyl groups having from 3 to 8 ring atoms, and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of alkyl groups having from 1 to 4 carbonatoms, such as the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cyclopentyl and cyclooctyl groups and substituted analogs thereof,especially the unsubstituted groups and those having at least one methylsubstituent;

27. cycloalkenyl groups having from 5 to 8 ring atoms, and which areunsubstituted or are substituted by at least one substituent selectedfrom the group consisting of alkyl groups having from 1 to 4 carbonatoms, such as the 1-cyclopenten-1-yl, 2-cyclopenten-1-yl,1-cyclohexen-1-yl, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl,1-cylohepten-1-yl, 2-cyclohepten-1-yl, 1-cycloocten-1-yl and3-cycloocten-1-yl groups and substituted analogs thereof, especially theunsubstituted groups and those having at least one methyl substituent;

28. tri-substituted silyl groups in which the substituents areindependently selected from the group consisting of alkyl groups havingfrom 1 to 6 carbon atoms and aryl groups having from 6 to 10 carbonatoms, preferably in which all three or two or one of the substituentsare alkyl groups having from 1 to 5, more preferably from 1 to 4, carbonatoms, and none, one or two of the substituents are aryl groups, asdefined above, but preferably phenyl or substituted phenyl groups,preferably: tri(lower alkyl)silyl groups (such as the trimethylsilyl,triethylsilyl, isopropyldimethylsilyl, t-butyl-dimethylsilyl,methyldiisopropylsilyl, methyldi-t-butylsilyl and triisopropylsilylgroups); and tri(lower alkyl)silyl groups in which one or two of thealkyl groups have been replaced by aryl groups (such as thediphenylmethylsilyl, diphenylbutyl-silyl, diphenyl-t-butylsilyl,diphenylisopropylsilyl and phenyldiisopropylsilyl groups);

29. heterocyclic groups which have 5 or 6 ring atoms, of which from 1 to3 are selected from the group consisting of nitrogen, oxygen and sulfurhetero-atoms, said heterocyclic group being unsubstituted or beingsubstituted by at least one substituent selected from the groupconsisting of substituents (c), defined below, such as those definedabove in relation to the groups which may be represented by R³ ; and

30. halogen atoms, such as the chlorine, fluorine, bromine and iodineatoms.

Examples of the groups and atoms which may be included in substituents(b) include:

alkyl groups having from 1 to 8 carbon atoms, such as the methyl, ethyl,propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl,3-methylbutyl, 2,2-dimethylpropyl, 1,1-dimethylpropyl, hexyl,1-methylpentyl, 4-methylpentyl, heptyl, 1-methylhexyl, 2-methylhexyl,5-methylhexyl, 3-ethylpentyl, octyl, 2-methylheptyl, 6-methylheptyl,2-ethylhexyl, 2-ethyl-3-methylpentyl and 3-ethyl-2-methylpentyl groups;and

hydroxy, alkoxy, aryl, aryloxy, aliphatic acyloxy, aromatic acyloxy,carboxy, alkoxycarbonyl, aryloxycarbonyl, mercapto, alkylthio, arylthio,aralkylthio, aralkyldithio, aryldithio, alkyldithio, alkylsulfinyl,arylsulfonyl, alkylsulfonyl, arylsulfonyl, cyano, aliphatic and aromaticacyl and heterocyclic groups and groups of formula --NR⁴ R⁵, --CONHR⁴ R⁵and --OCONHR⁴ R⁵, and halogen atoms, as exemplified in relation tosubstituents (a).

Substituent (c) may be an oxygen atom, to form an oxo group (>C═O) withthe carbon atom to which it is attached, or it may be various othergroups and atoms, as exemplified in relation to substituents (a) and(b).

Many of the compounds of the present invention have the anti-tumoractivity referred to above. Others may be of value as intermediates inthe preparation of other compounds of the present invention, which mayhave a greater activity.

Preferred classes of compounds of the present invention include thosecompounds of formula (I) in which R¹ and R² each represents a group offormula R³ --CO-- and the groups represented by R³ are the same ordifferent and each is selected from the group consisting of:

unsubstituted alkyl groups having from 9 to 20 carbon atoms;

substituted alkyl groups having from 10 to 20 carbon atoms andsubstituted by at least one substituent selected from the groupconsisting of substituents (d), defined below;

unsubstituted alkenyl groups having from 9 to 20 carbon atoms;

substituted alkenyl groups having from 10 to 20 carbon atoms andsubstituted by at least one substituent selected from the groupconsisting of substituents (d), defined below;

unsubstituted alkynyl groups having from 8 to 10 carbon atoms; and

substituted alkynyl groups having from 8 to 10 carbon atoms andsubstituted by at least one substituent selected from the groupconsisting of substituents (d), defined below;

substituents (d):

hydroxy groups, protected hydroxy groups, amino groups, protected aminogroups, groups of formula --NR⁶ R⁷, where:

R⁶ and R⁷ are independently selected from the group consisting of alkylgroups having from 1 to 4 carbon atoms, alkylcarbonyl groups having atotal of from 2 to 5 carbon atoms, benzoyl groups, substituted benzoylgroups in which the substituents are selected from the group consistingof substituents (b), defined above, alkoxycarbonyl groups having from 2to 5 carbon atoms, phenoxycarbonyl groups and substitutedphenoxycarbonyl groups in which the substituents are selected from thegroup consisting of substituents (b), defined above;

carboxy groups, protected carboxy groups, mercapto groups, protectedmercapto groups, alkoxy groups having from 1 to 8 carbon atoms,alkylthio groups having 1 or 2 carbon atoms, phenyl groups, substitutedphenyl groups in which the substituents are selected from the groupconsisting of substituents (b), defined above, phenoxy groups,substituted phenoxy groups in which the substituents are selected fromthe group consisting of substituents (b), defined above,alkylcarbonyloxy groups having from 2 to 9 carbon atoms, benzoyloxygroups, nitro groups, alkoxycarbonyl groups having from 2 to 5 carbonatoms, carbamoyl groups, alkylthio groups having from 1 to 8 carbonatoms, phenylthio groups, alkylthio groups having 1 or 2 carbon atomsand substituted by a phenyl group, alkyldithio groups having 1 or 2carbon atoms and substituted by a phenyl group, phenyldithio groups,alkyldithio groups having from 1 to 8 carbon atoms, alkylsulfinyl groupshaving from 1 to 8 carbon atoms, phenylsulfinyl groups, alkylsulfonylgroups having from 1 to 8 carbon atoms, phenylsulfonyl groups, cyanogroups, alkylcarbonyl groups having from 2 to 9 carbon atoms, benzoylgroups, carbamoyloxy groups, heterocyclic groups having 5 or 6 ringatoms, of which 1 is a hetero-atom selected from the group consisting ofnitrogen, oxygen and sulfur hetero-atoms, and halogen atoms.

More preferred classes of compounds of the present invention includethose compounds of formula (I) in which R¹ and R² each represents agroup of formula R³ --CO-- and the groups represented by R³ are the sameor different and each is selected from the group consisting of:

unsubstituted alkyl groups having from 9 to 20 carbon atoms;

substituted alkyl groups having from 10 to 20 carbon atoms andsubstituted by at least one substituent selected from the groupconsisting of substituents (e), defined below;

unsubstituted alkenyl groups having from 9 to 20 carbon atoms;

substituted alkenyl groups having from 10 to 20 carbon atoms andsubstituted by at least one substituent selected from the groupconsisting of substituents (e), defined below;

unsubstituted alkynyl groups having from 8 to 10 carbon atoms; and

substituted alkynyl groups having from 8 to 10 carbon atoms andsubstituted by at least one substituent selected from the groupconsisting of substituents (e), defined below;

substituents (e):

hydroxy groups, protected hydroxy groups, amino groups, protected aminogroups, carboxy groups, protected carboxy groups, mercapto groups,protected mercapto groups, alkoxy groups having from 1 to 8 carbon atomsand alkylthio groups having 1 or 2 carbon atoms.

The most preferred classes of compounds of the present invention includethose compounds of formula (I) in which R¹ and R² each represents agroup of formula R³ --CO-- and the groups represented by R³ are the sameor different and each is selected from the group consisting of:

unsubstituted alkyl groups having from 9 to 20 carbon atoms; and

unsubstituted alkenyl groups having from 9 to 20 carbon atoms.

In any of the compounds of the present invention which contains ahydroxy, amino, mercapto or carboxy group, any of these groups may beprotected by a suitable protecting group. Where the protecting group ison a compound intended for use merely as a chemical intermediate, itsnature is not critical to the invention and any of the well knownprotecting groups may be employed. Where the resulting compound isintended for therapeutic use, the protecting group should bepharmaceutically acceptable.

Examples of hydroxy-protecting groups include:

1. aliphatic acyl groups, e.g.: alkylcarbonyl groups preferably havingfrom 1 to 20 carbon atoms, such as the formyl, acetyl, propionyl,butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl,lauroyl, myristoyl, tridecanoyl, palmitoyl and stearoyl groups;haloalkylcarbonyl groups, especially the haloacetyl groups, such as thechloroacetyl, dichloroacetyl, trichloroacetyl and trifluoroacetylgroups; lower alkoxyalkylcarbonyl groups, especially those having from 3to 7 carbon atoms, such as the methoxyacetyl group; unsaturatedalkylcarbonyl groups, such as the (E)-2-methyl-2-butenoyl group;

2. aromatic acyl groups, especially the arylcarbonyl groups, such as thebenzoyl, α-naphthoyl and β-naphthoyl groups; haloarylcarbonyl groups,such as the 2-bromobenzoyl and 4-chlorobenzoyl groups; loweralkylarylcarbonyl groups, especially those in which the alkyl part hasfrom 1 to 4 carbon atoms and the aryl part is a phenyl group, such asthe 2,4,6-trimethylbenzoyl and 4-toluoyl groups; loweralkoxyarylcarbonyl groups, especially those in which the alkoxy part hasfrom 1 to 4 carbon atoms and the aryl part is a phenyl group, such asthe 4-anisoyl group; nitroarylcarbonyl groups, especially those in whichthe aryl part is a phenyl group, such as the 4-nitrobenzoyl and2-nitrobenzoyl groups; lower alkoxycarbonylarylcarbonyl groups,especially those in which the alkoxy part has from 1 to 4 carbon atomsand the aryl part is a phenyl group, such as the2-(methoxycarbonyl)benzoyl group; arylarylcarbonyl groups, especiallythose in which each aryl part is an optionally substituted phenyl group,such as the 4-phenylbenzoyl group;

3. tetrahydropyranyl and tetrahydrothiopyranyl groups, such as thetetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl,4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl and4-methoxytetrahydrothiopyran-4-yl groups;

4. tetrahydrofuranyl and tetrahydrothienyl groups, such as thetetrahydrofuran-2-yl and tetrahydrothien-2-yl groups;

5. silyl groups, especially: tri-lower-alkylsilyl groups, such as thetrimethylsilyl, triethylsilyl, isopropyldimethylsilyl,t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl andtriisopropylsilyl groups; and tri-lower-alkylsilyl groups in which 1 or2 of the alkyl groups has been replaced by an aryl groups, such as thediphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl andphenyldiisopropylsilyl groups;

6. alkoxymethyl groups, especially lower alkoxymethyl groups, such asthe methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl,propoxymethyl, isopropoxymethyl, butoxymethyl and t-butoxymethyl groups;lower alkoxy-lower-alkoxymethyl groups, especially such groups in whicheach of the alkoxy parts has from 1 to 4 carbon atoms, such as the2-methoxyethoxymethyl; halogen-substituted lower-alkoxymethyl groups,such as the 2,2,2-trichloroethoxymethyl andbis(2-chloroethoxy)methylgroups;

7. substituted ethyl groups, especially the lower alkoxyethyl groups,such as the 1-ethoxyethyl and 1-(isopropoxy)ethyl groups; haloethylgroups, such as the 2,2,2-trichloroethyl group; arylselenylethyl groups,such as the 2-(phenylselenyl)ethyl group;

8. aralkyl groups, and especially lower (e.g. having from 1 to 4 carbonatoms) alkyl groups which are substituted by from 1 to 3 aryl groups(especially having from 6 to 10 ring atoms), such as the benzyl,α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl,α-naphthyldiphenylmethyl and 9-anthrylmethyl groups; and such groups inwhich the aryl part is substituted with such substituent(s) as loweralkyl, lower alkoxy, nitro, halogen or cyano group(s), such as the4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl,4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl,4,4'-dimethoxytriphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl,4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl,4-cyanobenzyldiphenylmethyl, bis(2-nitrophenyl)methyl and piperonylgroups;

9. alkoxycarbonyl groups, including: lower alkoxycarbonyl groups, suchas the methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl andisobutoxycarbonyl groups; lower alkoxycarbonyl group substituted by atleast one halogen atom or tri(lower alkyl)silyl group, such as the2,2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl groups;

10. alkenyloxycarbonyl groups, such as the vinyloxycarbonyl andallyloxycarbonyl groups;

11. aralkyloxycarbonyl group in which the alkyl part preferably has from1 to 4 carbon atoms and the aryl part or parts preferably has from 6 to10 ring carabon atoms and which may optionally have 1 or 2 suchsubstituents as lower alkoxy and/or nitro groups on its aryl ring, suchas the benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl,3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl and4-nitrobenzyloxycarbonyl groups.

The hydroxy-protecting groups mentioned above are for protection of thehydroxy group during a reaction. In addition to these, there may bementioned protecting groups which can easily be hydrolyzed in vivo whenadministered to living body and which may be used for making a pro-drug,such as the pivaloyloxymethoxycarbonyl group.

Examples of amino-protecting group, although equally not particularlylimited, include:

1. aliphatic acyl groups, including: alkylcarbonyl groups, such as theformyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl,valeryl, isovaleryl, octanoyl, lauroyl, myristoyl, tridecanoyl,palmitoyl and stearoyl groups; haloaliphatic acyl groups, such as thechloroacetyl, dichloroacetyl, trichloroacetyl and trifluoroacetylgroups; lower alkoxyaliphatic acyl groups, such as the methoxyacetylgroup; and unsaturated aliphatic acyl groups, such as the(E)-2-methyl-2-butenoyl group;

2. aromatic acyl groups, including: the arylcarbonyl groups, such as thebenzoyl, α-naphthoyl and β-naphthoyl groups; haloarylcarbonyl groups,such as the 2-bromobenzoyl and 4-chlorobenzoyl groups; loweralkylarylcarbonyl groups, such as the 2,4,6-trimethylbenzoyl and4-toluoyl groups; lower alkoxyarylcarbonyl groups, such as the 4-anisoylgroup; nitroarylcarbonyl groups, such as the 4-nitrobenzoyl and2-nitrobenzoyl groups; lower alkoxycarbonylarylcarbonyl groups, such asthe 2-(methoxycarbonyl)benzoyl group; and arylarylcarbonyl groups, suchas the 4-phenylbenzoyl group;

3. alkoxycarbonyl groups, including: the lower alkoxycarbonyl groups,such as the methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl andisobutoxycarbonyl groups; lower alkoxycarbonyl groups substituted by oneor more halogen atoms and/or tri(lower alkyl)silyl groups, such as the2,2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl groups;

4. alkenyloxycarbonyl groups, such as the vinyloxycarbonyl andallyloxycarbonyl groups;

5. aralkyloxycarbonyl groups which may optionally be substituted by 1 or2 lower alkoxy groups or nitro groups on its aryl ring, such as thebenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl,3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl and4-nitrobenzyloxycarbonyl groups;

6. silyl groups, including: tri(lower alkyl)silyl groups, such as thetrimethylsilyl, triethylsilyl, isopropyldimethylsilyl,t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl andtriisopropylsilyl groups; tri(lower alkyl)silyl groups in which 1 or 2of the alkyl groups has been replaced by 1 or 2 aryl groups, such as thediphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl andphenyldiisopropylsilyl groups;

7. aralkyl groups, including: lower alkyl groups substituted by from 1to 3 aryl groups, such as the benzyl, phenethyl, 3-phenylpropyl,α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl,α-naphthyldiphenylmethyl and 9-anthrylmethyl groups, and such groups inwhich the aryl part is substituted by such substituents as lower alkyl,lower alkoxy, nitro and cyano groups and halogen atoms, such as the4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl,4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl,4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl,4-cyanobenzyldiphenylmethyl, bis(2-nitrophenyl)methyl and piperonylgroups; and

8. substituted methylene groups capable of forming a Schiff base, suchas the N,N-dimethylaminomethylene, benzylidene, 4-methoxybenzylidene,4-nitrobenzylidene, salicylidene, 5-chlorosalicylidene,diphenylmethylene and (5-chloro-2-hydroxyphenyl)phenylmethylene groups.

Examples of mercapto-protecting groups include:

1. aralkyl groups, including monoarylalkyl groups, such as the benzyl,p-methoxybenzyl and p-nitrobenzyl groups; di- and tri-arylmethyl groups,such as the diphenylmethyl, 4,4'-dimethoxydiphenylmethyl and tritylgroups;

2. pyranyl groups, such as the 2-tetrahydropyranyl group;

3. aliphatic and aromatic acyl groups, such as the acetyl and benzoylgroups;

4. aralkyloxycarbonyl groups, such as the benzyloxycarbonyl andp-methoxybenzyloxycarbonyl groups;

5. alkoxycarbonyl groups, such as the t-butoxycarbonyl group; and

6. pyridinesulfenyl groups, such as the S-2-pyridinesulfenyl andS-3-nitro-2-pyridinesulfenyl groups.

Examples of suitable carboxy-protecting groups which may be used forprotection during a reaction include:

1. lower alkyl groups, such as the methyl, ethyl, propyl, isopropyl,butyl, isobutyl, sec-butyl, t-butyl, pentyl and hexyl groups;

2. halogenated lower alkyl groups, such as the 2,2,2-trichloroethyl,2-bromoethyl, 2-chloroethyl, 2-fluoroethyl and 2,2-dibromoethyl groups;

3. aralkyl groups, including: lower alkyl groups substituted by from 1to 3 aryl groups, such as the benzyl, phenethyl, 3-phenylpropyl,α-naphtylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl,α-naphthyldiphenylmethyl and 9-anthrylmethyl groups and such groups inwhich the aryl part is substituted by such substituents as lower alkyl,lower alkoxy, nitro, halogen and cyano groups and atoms, for example the4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl,4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl,4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl,4-cyanobenzyldiphenylmethyl, bis(2-nitrophenyl)methyl and piperonylgroups.

Alternatively, a carboxy-protecting group able to be hydrolyzed in vivoand so usable for preparing a pro-drug for administration to the livingbody may be used, for example:

1. alkoxymethyl groups, including: lower alkoxymethyl groups, such asthe methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl,propoxymethyl, isopropoxymethyl, butoxymethyl and t-butoxymethyl groups;lower-alkoxy-lower-alkoxymethyl groups, such as the2-methoxyethoxymethyl group; halogenated lower alkoxymethyl groups, suchas the 2,2,2-trichloroethoxymethyl and bis(2-chloroethoxy)methyl groups;

2. substituted ethyl groups, including: lower alkoxyethyl groups, suchas the 1-ethoxyethyl, 1-methyl-1-methoxyethyl and 1-(isopropoxy)ethylgroups; haloethyl groups, such as the 2,2,2-trichloroethyl groups; andarylselenylethyl groups, such as the 2-(phenylselenyl)ethyl group;

3. aliphatic acyloxymethyl groups, such as the acetoxymethyl,propionyloxymethyl, butyryloxymethyl and pivaloyloxymethyl groups;

4. 1-lower-alkoxycarbonyloxyethyl groups, such as the1-methoxycarbonyloxyethyl, 1-ethoxycarbonyloxyethyl,1-propoxycarbonyloxyethyl, 1-isopropoxycarbonyloxyethyl,1-butoxycarbonyloxyethyl 1-isobutoxycarbonyloxyethyl and1-cyclohexyloxycarbonyloxyethyl groups;

5. the cyclohexyloxycarbonyloxy(cyclohexyl)methyl group;

6. the phthalidyl group; and

7. the (2-oxo-5-methyl-1,3-dioxolen-4-yl)methyl group.

The compounds of the invention may contain asymmetric carbon atomsand/or carbon-carbon double bonds and can, therefore, form opticaland/or cis/trans isomers. Although these are all referred to herein by asingle formula, the present invention envisages both mixtures of theisomers (whether as obtained in the course of synthesis or by mixing)and the individual isolated isomers (which may be prepared bystereo-specific synthesis techniques or by separation of a synthesisedmixture using conventional methods).

Examples of specific compounds of the present invention are thosecompounds of formula (I), given above, in which R¹ and R² are as definedin the following Table 1. In the Table, the following abbreviations areused to refer to certain substituent groups:

    ______________________________________                                        Ac              acetyl                                                        Aoc             allyloxycarbonyl                                              Boz             benzoyl                                                       Bu              butyl                                                         cBu             cyclobutyl                                                    Byr             butyryl                                                       Bz              benzyl                                                        Car             carbamoyl                                                     Dco             decanoyl                                                      Ddc             dodecyl                                                       Et              ethyl                                                         Etc             ethoxycarbonyl                                                Fmoc            fluoenylmethoxycarbonyl                                       Fur             furyl                                                         cHex            cyclohexenyl                                                  cHp             cycloheptyl                                                   Hpo             heptanoyl                                                     Hx              hexyl                                                         cHx             cyclohexyl                                                    Hxo             hexanoyl                                                      Ind             indolyl                                                       Isox            isoxazolyl                                                    Me              methyl                                                        Mec             methoxycarbonyl                                               Mem             methoxyethoxymethyl                                           Mom             methoxymethyl                                                 Mor             morpholino                                                    Np              naphthyl                                                      Oc              octyl                                                         cOc             cyclooctyl                                                    cPen            cyclopentenyl                                                 Ph              phenyl                                                        Pip             piperidyl                                                     Piz             piperazinyl                                                   Pn              pentyl                                                        cPn             cyclopentyl                                                   Pr              propyl                                                        cPr             cyclopropyl                                                   Prn             propionyl                                                     Pyr             pyridyl                                                       Pyrd            pyrrolidinyl                                                  Retio           retinoyl                                                      Thi             thienyl                                                       Thiz            thiazolyl                                                     Troc            trichloroethoxycarbonyl                                       ______________________________________                                    

                                      TABLE 1                                     __________________________________________________________________________    Cpd.                                                                          No.                                                                              R.sup.1          R.sup.2                                                   __________________________________________________________________________     1 CH.sub.3 CH.sub.2 CO--                                                                         CH.sub.3 CH.sub.2 CO--                                     2 CH.sub.3 CH.sub.2 CO--                                                                         H                                                          3 H                CH.sub.3 CH.sub.2 CO--                                     4 CH.sub.3 CH.sub.2 CH.sub.2 CO--                                                                CH.sub.3 CH.sub.2 CH.sub.2 CO--                            5 CH.sub.3 (CH.sub.2).sub.3 CO--                                                                 CH.sub.3 (CH.sub.2).sub.3 CO--                             6 CH.sub.3 (CH.sub.2).sub.4 CO--                                                                 CH.sub.3 (CH.sub.2).sub.4 CO--                             7 CH.sub.3 (CH.sub.2).sub.5 CO--                                                                 CH.sub.3 (CH.sub.2).sub.5 CO--                             8 H                CH.sub.3 (CH.sub.2).sub.5 CO--                             9 CH.sub.3 (CH.sub.2).sub.6 CO--                                                                 CH.sub.3 (CH.sub.2).sub.6 CO--                             10                                                                              H                CH.sub.3 (CH.sub.2).sub.6 CO--                             11                                                                              CH.sub.3 (CH.sub.2).sub.7 CO--                                                                 CH.sub.3 (CH.sub.2).sub.7 CO--                             12                                                                              H                CH.sub.3 (CH.sub.2).sub.7 CO--                             13                                                                              CH.sub.3 (CH.sub.2).sub.8 CO--                                                                 CH.sub.3 (CH.sub.2).sub.8 CO--                             14                                                                              H                CH.sub.3 (CH.sub.2).sub.8 CO--                             15                                                                              CH.sub.3 (CH.sub.2).sub.9 CO--                                                                 CH.sub.3 (CH.sub.2).sub.9 CO--                             16                                                                              H                CH.sub.3 (CH.sub.2).sub.9 CO--                             17                                                                              CH.sub.3 (CH.sub.2).sub.10 CO--                                                                CH.sub.3 (CH.sub.2).sub.10 CO--                            18                                                                              H                CH.sub.3 (CH.sub.2).sub.10 CO--                            19                                                                              CH.sub.3 (CH.sub.2).sub.11 CO--                                                                CH.sub.3 (CH.sub.2).sub.11 CO--                            20                                                                              H                CH.sub.3 (CH.sub.2).sub.11 CO--                            21                                                                              CH.sub.3 (CH.sub.2).sub.12 CO--                                                                CH.sub.3 (CH.sub.2).sub.12 CO--                            22                                                                              H                CH.sub.3 (CH.sub.2).sub.12 CO--                            23                                                                              CH.sub.3 (CH.sub.2).sub.13 CO--                                                                CH.sub.3 (CH.sub.2).sub.13 CO--                            24                                                                              H                CH.sub.3 (CH.sub.2).sub.13 CO--                            25                                                                              CH.sub.3 (CH.sub.2).sub.14 CO--                                                                CH.sub.3 (CH.sub.2).sub.14 CO--                            26                                                                              CH.sub.3 (CH.sub.2).sub.14 CO--                                                                H                                                          27                                                                              H                CH.sub.3 (CH.sub.2).sub.14 CO--                            28                                                                              CH.sub.3 (CH.sub.2).sub.15 CO--                                                                CH.sub.3 (CH.sub.2).sub.15 CO--                            29                                                                              CH.sub.3 (CH.sub.2).sub.15 CO--                                                                H                                                          30                                                                              H                CH.sub.3 (CH.sub.2).sub.15 CO--                            31                                                                              CH.sub.3 (CH.sub.2).sub.16 CO--                                                                CH.sub.3 (CH.sub.2).sub.16 CO--                            32                                                                              CH.sub.3 (CH.sub.2).sub.16 CO--                                                                H                                                          33                                                                              H                CH.sub.3 (CH.sub.2).sub.16 CO--                            34                                                                              CH.sub.3 (CH.sub.2).sub.17 CO--                                                                CH.sub.3 (CH.sub.2).sub.17 CO--                            35                                                                              H                CH.sub.3 (CH.sub.2).sub.17 CO--                            36                                                                              CH.sub.3 (CH.sub.2).sub.18 CO--                                                                CH.sub.3 (CH.sub.2).sub.18 CO--                            37                                                                              H                CH.sub.3 (CH.sub.2).sub.18 CO--                            38                                                                              CH.sub.3 (CH.sub.2).sub.19 CO--                                                                CH.sub.3 (CH.sub.2).sub.19 CO--                            39                                                                              H                CH.sub.3 (CH.sub.2).sub.19 CO--                            40                                                                              CH.sub.3 (CH.sub.2).sub.20 CO--                                                                CH.sub.3 (CH.sub.2).sub.20 CO--                            41                                                                              H                CH.sub.3 (CH.sub.2).sub.20 CO--                            42                                                                              (CH.sub.3).sub.2 CHCH.sub.2 CO--                                                               (CH.sub.3).sub.2 CHCH.sub.2 CO--                           43                                                                              H                (CH.sub.3).sub.2 CHCH.sub.2 CO--                           44                                                                              (CH.sub.3).sub.3 CCO--                                                                         (CH.sub.3).sub.3 CCO--                                     45                                                                              H                (CH.sub.3).sub.3 CCO--                                     46                                                                              CH.sub.2 ═CHCH.sub.2 CO--                                                                  CH.sub.2 ═CHCH.sub.2 CO--                              47                                                                              H                CH.sub.2 ═CHCH.sub.2 CO--                              48                                                                              CH.sub.3 CH═CHCO--                                                                         CH.sub.3 CH═CHCO--                                     49                                                                              H                CH.sub.3 CH═CHCO--                                     50                                                                              (CH.sub.3).sub.2 ═CHCO--                                                                   (CH.sub.3).sub.2 ═CHCO--                               51                                                                              H                (CH.sub.3).sub.2 ═CHCO--                               52                                                                              EtCH═CHCO--  EtCH═CHCO--                                            53                                                                              H                EtCH═CHCO--                                            54                                                                              H.sub.2 C═CHCH.sub.2 CH.sub.2 CO--                                                         H.sub.2 C═CHCH.sub.2 CH.sub.2 CO--                     55                                                                              H                H.sub.2 C═CHCH.sub.2 CH.sub.2 CO--                     56                                                                              PrCH═CHCO--  PrCH═CHCO--                                            57                                                                              H                PrCH═CHCO--                                            58                                                                              EtCH═CHCH.sub.2 CO--                                                                       EtCH═CHCH.sub.2 CO--                                   59                                                                              H                EtCH═CHCH.sub.2 CO--                                   60                                                                              PnCH═CHCO--  PnCH═CHCO--                                            61                                                                              H                PnCH═CHCO--                                            62                                                                              HxCH═CHCO--  HxCH═CHCO--                                            63                                                                              H                HxCH═CHCO--                                            64                                                                              H.sub.2 C═CH(CH.sub.2).sub.7 CO--                                                          H.sub.2 C═CH(CH.sub.2).sub.7 CO--                      65                                                                              H                H.sub.2 C═CH(CH.sub.2).sub.7 CO--                      66                                                                              H.sub.2 C═CH(CH.sub.2).sub.8 CO--                                                          H.sub.2 C═CH(CH.sub.2).sub.8 CO--                      67                                                                              H                H.sub.2 C═CH(CH.sub.2).sub.8 CO--                      68                                                                              BuCH═CH(CH.sub.2).sub.7 CO--                                                               BuCH═CH(CH.sub.2).sub.7 CO--                           69                                                                              H                BuCH═CH(CH.sub.2).sub.7 CO--                           70                                                                              HxCH═CH(CH.sub.2).sub.7 CO--                                                               HxCH═CH(CH.sub.2).sub.7 CO--                           71                                                                              H                HxCH═CH(CH.sub.2).sub.7 CO--                           72                                                                              OcCH═CH(CH.sub.2).sub.7 CO--                                                               OcCH═CH(CH.sub.2).sub.7 CO--                           73                                                                              H                OcCH═CH(CH.sub.2).sub.7 CO--                           74                                                                              Bu(CH.sub.2 CH═CH).sub.2 (CH.sub.2).sub.7 CO--                                             Bu(CH.sub.2 CH═CH).sub.2 (CH.sub.2).sub.7 CO--         75                                                                              H                Bu(CH.sub.2 CH═CH).sub.2 (CH.sub.2).sub.7 CO--         76                                                                              Me(CH.sub.2 CH═CH).sub.3 (CH.sub.2).sub.7 CO--                                             Me(CH.sub.2 CH═CH).sub.3 (CH.sub.2).sub.7 CO--         77                                                                              H                Me(CH.sub.2 CH═CH).sub.3 (CH.sub.2).sub.7 CO--         78                                                                              Bu(CH.sub.2 CH═CH).sub.3 (CH.sub.2).sub.4 CO--                                             Bu(CH.sub.2 CH═CH).sub.3 (CH.sub.2).sub.4 CO--         79                                                                              Pn(CH═CHCH.sub.2).sub.4 (CH.sub.2).sub.2 CO--                                              Pn(CH═CHCH.sub.2).sub.4 (CH.sub.2).sub.2 CO--          80                                                                              Me(CH.sub.2 CH═CH).sub.6 (CH.sub.2).sub.2 CO--                                             Me(CH.sub.2 CH═CH).sub.6 (CH.sub.2).sub.2 CO--         81                                                                              H                Pn(CH═CHCH.sub.2).sub.4 (CH.sub.2).sub.2 CO--          82                                                                              HxC(OH)H--CH.sub.2 CH═CHCO--                                                               HxC(OH)H--CH.sub.2 CH═CHCO--                           83                                                                              H                HxC(OH)H--CH.sub.2 CH═CHCO--                           84                                                                              HOCH.sub.2 (CH.sub.2).sub.14 CO--                                                              HOCH.sub.2 (CH.sub.2).sub.14 CO--                          85                                                                              H                HOCH.sub.2 (CH.sub.2).sub.14 CO--                          86                                                                              (4-MeOPh).sub.2 PhC--OCH.sub.2 (CH.sub.2).sub.14 CO--                                          (4-MeOPh).sub.2 PhC--OCH.sub.2 (CH.sub.2).sub.14                              CO--                                                       87                                                                              H                (4-MeOPh).sub.2 PhC--OCH.sub.2 (CH.sub.2).sub.14                              CO--                                                       88                                                                              HC.tbd.C.CO      HC.tbd.C.CO                                                89                                                                              H                HC.tbd.C.CO                                                90                                                                              MeC.tbd.C.CO     MeC.tbd.C.CO                                               91                                                                              H                MeC.tbd.C.CO                                               92                                                                              PnC.tbd.C.CO     PnC.tbd.C.CO                                               93                                                                              H                PnC.tbd.C.CO                                               94                                                                              MeOCH.sub.2.CO   MeOCH.sub.2.CO                                             95                                                                              MeOCH.sub.2.CO   H                                                          96                                                                              H                MeOCH.sub.2.CO                                             97                                                                              DdcOCH.sub.2 CH.sub.2.CO                                                                       DdcOCH.sub.2 CH.sub.2.CO                                   98                                                                              H                DdcOCH.sub.2 CH.sub.2.CO                                   99                                                                              MeO(CH.sub.2).sub.9.CO                                                                         MeO(CH.sub.2).sub.9.CO                                    100                                                                              MeO(CH.sub.2).sub.11.CO                                                                        MeO(CH.sub.2).sub.11.CO                                   101                                                                              MeO(CH.sub.2).sub.13.CO                                                                        MeO(CH.sub.2).sub.13.CO                                   102                                                                              MeO(CH.sub.2).sub.15.CO                                                                        MeO(CH.sub.2).sub.15.CO                                   103                                                                              H                MeO(CH.sub.2).sub.13.CO                                   104                                                                              PhOCH.sub.2.CO   PhOCH.sub.2.CO                                            105                                                                              H                PhOCH.sub.2.CO                                            106                                                                              Bz.CO            Bz.CO                                                     107                                                                              H                Bz.CO                                                     108                                                                              2-PhPrn          2-PhPrn                                                   109                                                                              H                2-PhPrn                                                   110                                                                              3-PhPrn          3-PhPrn                                                   111                                                                              H                3-PhPrn                                                   112                                                                              6-PhHxo          6-PhHxo                                                   113                                                                              PhCH═CH.CO   PhCH═CH.CO                                            114                                                                              H                PhCH═CH.CO                                            115                                                                              β--Np.CH.sub.2.CO                                                                         β--Np.CH.sub.2.CO                                    116                                                                              H                β--Np.CH.sub.2.CO                                    117                                                                              Boz              Boz                                                       118                                                                              H                Boz                                                       119                                                                              2-Fur.CO         2-Fur.CO                                                  120                                                                              H                2-Fur.CO                                                  121                                                                              2-Fur.CH═CH.CO                                                                             2-Fur.CH═CH.CO                                        122                                                                              3-Thi.CO         3-Thi.CO                                                  123                                                                              H                3-Thi.CO                                                  124                                                                              2-Thi.CH═CH.CO                                                                             2-Thi.CH═CH.CO                                        125                                                                              3-Thi.CO         H                                                         126                                                                              2-Thi.CO         2-Thi.CO                                                  127                                                                              H                2-Thi.CO                                                  128                                                                              2-ThiCH.sub.2.CO 2-ThiCH.sub.2.CO                                          129                                                                              H                2-ThiCH.sub.2.CO                                          130                                                                              2-NH.sub.2 -4-Thiz.CH.sub.2.CO                                                                 2-NH.sub.2 -4-Thiz.CH.sub.2.CO                            131                                                                              H                2-NH.sub.2 -4-Thiz.CH.sub.2.CO                            132                                                                              5-oxo-2-Pyrd.CO  5-oxo-2-Pyrd.CO                                           133                                                                              H                5-oxo-2-Pyrd.CO                                           134                                                                              3-Isox.CO        3-Isox.CO                                                 135                                                                              H                3-Isox.CO                                                 136                                                                              4-Isox.CO        4-Isox.CO                                                 137                                                                              H                4-Isox.CO                                                 138                                                                              6-oxo-2-Pip.CO   6-oxo-2-Pip.CO                                            139                                                                              H                6-oxo-2-Pip.CO                                            140                                                                              3-NH.sub.2 Prn   3-NH.sub.2 Prn                                            141                                                                              H                3-NH.sub.2 Prn                                            142                                                                              6-NH.sub.2 Hxo   6-NH.sub.2 Hxo                                            143                                                                              H                6-NH.sub.2 Hxo                                            144                                                                              H.sub.2 N(CH.sub.2).sub.11.CO                                                                  H.sub.2 N(CH.sub.2).sub.11.CO                             145                                                                              H.sub.2 N(CH.sub.2).sub.11.CO                                                                  H                                                         146                                                                              H.sub.2 N(CH.sub.2).sub.15.CO                                                                  H.sub.2 N(CH.sub.2).sub.15.CO                             147                                                                              H.sub.2 N(CH.sub.2).sub.15.CO                                                                  H                                                         148                                                                              TrocNH(CH.sub.2).sub.2.CO                                                                      TrocNH(CH.sub.2).sub.2.CO                                 149                                                                              TrocNH(CH.sub.2).sub.2.CO                                                                      H                                                         150                                                                              TrocNH(CH.sub.2).sub.5.CO                                                                      TrocNH(CH.sub.2).sub.5.CO                                 151                                                                              TrocNH(CH.sub.2).sub.5.CO                                                                      H                                                         152                                                                              TrocNH(CH.sub.2).sub.11.CO                                                                     TrocNH(CH.sub.2).sub.11.CO                                153                                                                              H                TrocNH(CH.sub.2).sub.11.CO                                154                                                                              TrocNH(CH.sub.2).sub.15.CO                                                                     TrocNH(CH.sub.2).sub.15.CO                                155                                                                              H                TrocNH(CH.sub.2).sub.15.CO                                156                                                                              AocNH(CH.sub.2).sub.2.CO                                                                       AocNH(CH.sub.2).sub.2.CO                                  157                                                                              H                AocNH(CH.sub.2).sub.2.CO                                  158                                                                              AocNH(CH.sub.2).sub.5.CO                                                                       AocNH(CH.sub.2).sub.5.CO                                  159                                                                              AocNH(CH.sub.2).sub.5.CO                                                                       H                                                         160                                                                              AocNH(CH.sub.2).sub.11.CO                                                                      AocNH(CH.sub.2).sub.11.CO                                 161                                                                              H                AocNH(CH.sub.2).sub.11.CO                                 162                                                                              AocNH(CH.sub.2).sub.15.CO                                                                      AocNH(CH.sub.2).sub.15.CO                                 163                                                                              H                AocNH(CH.sub.2).sub.15.CO                                 164                                                                              FmocNH(CH.sub.2).sub.11.CO                                                                     FmocNH(CH.sub.2).sub.11.CO                                165                                                                              Ph.sub.3 C.S.NH(CH.sub.2).sub.11.CO                                                            Ph.sub.3 C.S.NH(CH.sub.2).sub.11.CO                       166                                                                              ClCH.sub.2 CO    ClCH.sub.2 CO                                             167                                                                              H                ClCH.sub.2 CO                                             168                                                                              FCH.sub.2 CO     FCH.sub.2 CO                                              169                                                                              H                FCH.sub.2 CO                                              170                                                                              BrCH.sub.2 CO    BrCH.sub.2 CO                                             171                                                                              H                BrCH.sub.2 CO                                             172                                                                              BrCH.sub.2 CO    H                                                         173                                                                              ICH.sub.2 CO     ICH.sub.2 CO                                              174                                                                              ICH.sub.2 CO     H                                                         175                                                                              H                ICH.sub.2 CO                                              176                                                                              MeSCH.sub.2 CO   MeSCH.sub.2 CO                                            177                                                                              H                MeSCH.sub.2 CO                                            178                                                                              MeS(CH.sub.2).sub.2 CO                                                                         MeS(CH.sub.2).sub.2 CO                                    179                                                                              MeS(CH.sub.2).sub.9 CO                                                                         MeS(CH.sub.2).sub.9 CO                                    180                                                                              MeS(CH.sub.2).sub.11 CO                                                                        MeS(CH.sub.2).sub.11 CO                                   181                                                                              MeS(CH.sub.2).sub.15 CO                                                                        MeS(CH.sub.2).sub.15 CO                                   182                                                                              MeSO.sub.2 CH.sub.2 CO                                                                         MeSO.sub.2 CH.sub.2 CO                                    183                                                                              H                MeSO.sub.2 CH.sub.2 CO                                    184                                                                              MeSO.sub.2 (CH.sub.2).sub.9 CO                                                                 MeSO.sub.2 (CH.sub.2).sub.9 CO                            185                                                                              MeSO.sub.2 (CH.sub.2).sub.11 CO                                                                MeSO.sub.2 (CH.sub.2).sub.11 CO                           186                                                                              MeSO.sub.2 (CH.sub.2).sub.15 CO                                                                MeSO.sub.2 (CH.sub.2).sub.15 CO                           187                                                                              MeSO.CH.sub.2 CO MeSO.CH.sub.2 CO                                          188                                                                              H                MeSO.CH.sub.2 CO                                          189                                                                              MeSO(CH.sub.2).sub.9 CO                                                                        MeSO(CH.sub.2).sub.9 CO                                   190                                                                              MeSO(CH.sub.2).sub.11 CO                                                                       MeSO(CH.sub.2).sub.11 CO                                  191                                                                              MeSO(CH.sub.2).sub.15 CO                                                                       MeSO(CH.sub.2).sub.15 CO                                  192                                                                              HxS.CH.sub.2 CO  HxS.CH.sub.2 CO                                           193                                                                              H                HxS.CH.sub.2 CO                                           194                                                                              DdcS.CH.sub.2 CO DdcS.CH.sub.2 CO                                          195                                                                              H                DdcS.CH.sub.2 CO                                          196                                                                              PhS.CH.sub.2 CO  PhS.CH.sub.2 CO                                           197                                                                              H                PhS.CH.sub.2 CO                                           198                                                                              PhS(CH.sub.2).sub.9 CO                                                                         PhS(CH.sub.2).sub.9 CO                                    199                                                                              PhS(CH.sub.2).sub.11 CO                                                                        PhS(CH.sub.2).sub.11 CO                                   200                                                                              PhS(CH.sub.2).sub.15 CO                                                                        PhS(CH.sub.2).sub.15 CO                                   201                                                                              2-PhEt.S.CH.sub.2 CO                                                                           2-PhEt.S.CH.sub.2 CO                                      202                                                                              H                2-PhEt.S.CH.sub.2 CO                                      203                                                                              Bz.SS.CH.sub.2 CO                                                                              Bz.SS.CH.sub.2 CO                                         204                                                                              H                Bz.SS.CH.sub.2 CO                                         205                                                                              Bz.SS(CH.sub.2).sub.9 CO                                                                       Bz.SS(CH.sub.2).sub.9 CO                                  206                                                                              Bz.SS(CH.sub.2).sub.11 CO                                                                      Bz.SS(CH.sub.2).sub.11 CO                                 207                                                                              Bz.SS(CH.sub.2).sub.15 CO                                                                      Bz.SS(CH.sub.2).sub.15 CO                                 208                                                                              Et.sub.2 NCH.sub.2 CO                                                                          Et.sub.2 NCH.sub.2 CO                                     209                                                                              Et.sub.2 NCH.sub.2 CO                                                                          H                                                         210                                                                              Et.sub.2 N(CH.sub.2).sub.9 CO                                                                  Et.sub.2 N(CH.sub.2).sub.9 CO                             211                                                                              Et.sub.2 N(CH.sub.2).sub.11 CO                                                                 Et.sub.2 N(CH.sub.2).sub.11 CO                            212                                                                              Et.sub.2 N(CH.sub.2).sub.15 CO                                                                 Et.sub.2 N(CH.sub.2).sub.15 CO                            213                                                                              1-Me-4-Piz.CH.sub.2 CO                                                                         1-Me-4-Piz.CH.sub.2 CO                                    214                                                                              H                1-Me-4-Piz.CH.sub.2 CO                                    215                                                                              1-Me-4-Piz.(CH.sub.2).sub.15 CO                                                                1-Me-4-Piz.(CH.sub.2).sub.15 CO                           216                                                                              Me.sub.2 N(CH.sub.2).sub.9 CO                                                                  Me.sub.2 N(CH.sub.2).sub.9 CO                             217                                                                              Me.sub.2 N(CH.sub.2).sub.11 CO                                                                 Me.sub.2 N(CH.sub.2).sub.11 CO                            218                                                                              Me.sub.2 N(CH.sub.2).sub.15 CO                                                                 Me.sub.2 N(CH.sub.2).sub.15 CO                            219                                                                              4-Mor.CH.sub.2 CO                                                                              4-Mor.CH.sub.2 CO                                         220                                                                              4-Mor.CH.sub.2 CO                                                                              H                                                         221                                                                              4-Mor(CH.sub.2).sub.15 CO                                                                      4-Mor(CH.sub.2).sub.15 CO                                 222                                                                              4-Mor(CH.sub.2).sub.15 CO                                                                      H                                                         223                                                                              1-Pyrd.CH.sub.2 CO                                                                             1-Pyrd.CH.sub.2 CO                                        224                                                                              H                1-Pyrd.CH.sub.2 CO                                        225                                                                              1-Pyrd(CH.sub.2).sub.15 CO                                                                     1-Pyrd(CH.sub.2).sub.15 CO                                226                                                                              H                1-Pyrd(CH.sub.2).sub.15 CO                                227                                                                              Etc(CH.sub.2).sub.12 CO                                                                        Etc(CH.sub.2).sub.12 CO                                   228                                                                              H                Etc(CH.sub.2).sub.12 CO                                   229                                                                              Mec(CH.sub.2).sub.10 CO                                                                        Mec(CH.sub.2).sub.10 CO                                   230                                                                              Car(CH.sub.2).sub.12 CO                                                                        Car(CH.sub.2).sub.12 CO                                   231                                                                              H                Car(CH.sub.2).sub.12 CO                                   232                                                                              Car(CH.sub.2).sub.10 CO                                                                        Car(CH.sub.2).sub.10 CO                                   233                                                                              Car(CH.sub.2).sub.14 CO                                                                        Car(CH.sub.2).sub.14 CO                                   234                                                                              HOOC(CH.sub.2).sub.12 CO                                                                       HOOC(CH.sub.2).sub.12 CO                                  235                                                                              HOOC(CH.sub.2).sub.12 CO                                                                       H                                                         236                                                                              NC(CH.sub.2).sub.10 CO                                                                         NC(CH.sub.2).sub.10 CO                                    237                                                                              NC(CH.sub.2).sub.15 CO                                                                         NC(CH.sub.2).sub.15 CO                                    238                                                                              HO(CH.sub.2).sub.2 CO                                                                          HO(CH.sub.2).sub.2 CO                                     239                                                                              H                HO(CH.sub.2).sub.2 CO                                     240                                                                              HO(CH.sub.2).sub.5 CO                                                                          HO(CH.sub.2).sub.5 CO                                     241                                                                              H                HO(CH.sub.2).sub.5 CO                                     242                                                                              HO(CH.sub.2).sub.9 CO                                                                          HO(CH.sub.2).sub.9 CO                                     243                                                                              H                HO(CH.sub.2).sub.9 CO                                     244                                                                              HO(CH.sub.2).sub.11 CO                                                                         HO(CH.sub.2).sub.11 CO                                    245                                                                              H                HO(CH.sub.2).sub.11 CO                                    246                                                                              HO(CH.sub.2).sub.15 CO                                                                         HO(CH.sub.2).sub.15 CO                                    247                                                                              H                HO(CH.sub.2).sub.15 CO                                    248                                                                              MemO(CH.sub.2).sub.9 CO                                                                        MemO(CH.sub.2).sub.9 CO                                   249                                                                              MemO(CH.sub.2).sub.11 CO                                                                       MemO(CH.sub.2).sub.11 CO                                  250                                                                              MemO(CH.sub.2).sub.15 CO                                                                       MemO(CH.sub.2).sub.15 CO                                  251                                                                              MomO(CH.sub.2).sub.9 CO                                                                        MomO(CH.sub.2).sub.9 CO                                   252                                                                              MomO(CH.sub.2).sub.11 CO                                                                       MomO(CH.sub.2).sub.11 CO                                  253                                                                              MomO(CH.sub.2).sub.15 CO                                                                       MomO(CH.sub.2).sub.15 CO                                  254                                                                              HS(CH.sub.2).sub.2 CO                                                                          HS(CH.sub.2).sub.2 CO                                     255                                                                              HS(CH.sub.2).sub.2 CO                                                                          H                                                         256                                                                              HS(CH.sub.2).sub.5 CO                                                                          HS(CH.sub.2).sub.5 CO                                     257                                                                              HS(CH.sub.2).sub.5 CO                                                                          H                                                         258                                                                              HS(CH.sub.2).sub.11 CO                                                                         HS(CH.sub.2).sub.11 CO                                    259                                                                              HS(CH.sub.2).sub.11 CO                                                                         H                                                         260                                                                              HS(CH.sub.2).sub.15 CO                                                                         HS(CH.sub.2).sub.15 CO                                    261                                                                              HS(CH.sub.2).sub.15 CO                                                                         H                                                         262                                                                              Ac.S(CH.sub.2).sub.9 CO                                                                        Ac.S(CH.sub.2).sub.9 CO                                   263                                                                              Ac.S(CH.sub.2).sub.11 CO                                                                       Ac.S(CH.sub.2).sub.11 CO                                  264                                                                              Ac.S(CH.sub.2).sub.15 CO                                                                       Ac.S(CH.sub.2).sub.15 CO                                  265                                                                              4-PrBoz          4-PrBoz                                                   266                                                                              H                4-PrBoz                                                   267                                                                              4-PhByr          4-PhByr                                                   268                                                                              4-PhByr          H                                                         269                                                                              6-PhHxo          6-PhHxo                                                   270                                                                              6-PhHxo          H                                                         271                                                                              MecCH(NHAc).(CH.sub.2).sub.10 CO                                                               MecCH(NHAc).(CH.sub.2).sub.10 CO                          272                                                                              MecCH(NHAc).(CH.sub.2).sub.12 CO                                                               MecCH(NHAc).(CH.sub.2).sub.12 CO                          273                                                                              MecCH(NHAc).(CH.sub.2).sub.16 CO                                                               MecCH(NHAc).(CH.sub.2).sub.16 CO                          274                                                                              1-Ind.CO         1-Ind.CO                                                  275                                                                              1-Ind.CO         H                                                         276                                                                              1-(4H-cOc)CO     1-(4H-cOc)CO                                              277                                                                              1-(4H-cOc)CO     H                                                         278                                                                              2-PhOPrn         2-PhOPrn                                                  279                                                                              2-PhOPrn         H                                                         280                                                                              3-Pyr.CH═CHCO                                                                              3-Pyr.CH═CHCO                                         281                                                                              3-Pyr.CH═CHCO                                                                              H                                                         282                                                                              2-Pyr.CH.sub.2 CO                                                                              2-Pyr.CH.sub.2 CO                                         283                                                                              2-Pyr.CH.sub.2 CO                                                                              H                                                         284                                                                              2-HxDco          2-HxDco                                                   285                                                                              H                2-HxDco                                                   286                                                                              2-PnHpo          2-PnHpo                                                   287                                                                              H                2-PnHpo                                                   288                                                                              Me(CH.sub.2).sub.14 CO                                                                         Me(CH.sub.2).sub.16 CO                                    289                                                                              Me(CH.sub.2).sub.16 CO                                                                         Me(CH.sub.2).sub.14 CO                                    290                                                                              Me(CH.sub.2).sub.16 CO                                                                         OcCH═CH(CH.sub.2).sub.7 CO                            291                                                                              Me(CH.sub.2).sub.16 CO                                                                         Me(CH.sub.2).sub.12 CO                                    292                                                                              Me(CH.sub.2).sub.16 CO                                                                         CH.sub.2 ═CH(CH.sub.2).sub.8 CO                       293                                                                              cPrCO            cPrCO                                                     294                                                                              H                cPrCO                                                     295                                                                              cBuCO            cBuCO                                                     296                                                                              H                cBuCO                                                     297                                                                              cPnCO            cPnCO                                                     298                                                                              H                cPnCO                                                     299                                                                              cPnCO            H                                                         300                                                                              cHxCO            cHxCO                                                     301                                                                              H                cHxCO                                                     302                                                                              cHxCO            H                                                         303                                                                              cHpCO            cHpCO                                                     304                                                                              H                cHpCO                                                     305                                                                              cOcCO            H                                                         306                                                                              cOcCO            cOcCO                                                     307                                                                              H                cOcCO                                                     308                                                                              1-cPenCO         1-cPenCO                                                  309                                                                              H                1-cPenCO                                                  310                                                                              3-cHexCO         3-cHexCO                                                  311                                                                              H                3-cHexCO                                                  312                                                                              3-cHexCO         H                                                         313                                                                              4-cHexCO         4-cHexCO                                                  314                                                                              1-cHexCO         1-cHexCO                                                  315                                                                              2-HOcPnCO        2-HOcPnCO                                                 316                                                                              2-HOcPnCO        H                                                         317                                                                              4-NH.sub.2 cHxCO 4-NH.sub.2 cHxCO                                          318                                                                              4-NH.sub.2 cHxCO H                                                         319                                                                              2-ClcHxCO        2-ClcHxCO                                                 320                                                                              Retio            Retio                                                     321                                                                              H                Retio                                                     322                                                                              Retio            H                                                         323                                                                              Me(CH.sub.2).sub.14 CO                                                                         OcCH═CH(CH.sub.2).sub.7 CO                            324                                                                              Me(CH.sub.2).sub.14 CO                                                                         Me(CH.sub.2).sub.12 CO                                    325                                                                              Me(CH.sub.2).sub.14 CO                                                                         CH.sub.2 ═CH(CH.sub.2).sub.8 CO                       326                                                                              Me.sub.3 SiCH.sub.2 CH.sub.2 OCH.sub.2 O(CH.sub.2).sub.15 CO                                   Me.sub.3 SiCH.sub.2 CH.sub.2 OCH.sub.2 O(CH.sub.2).sub                        .15 CO                                                    327                                                                              MeSCH.sub.2 O(CH.sub.2).sub.9 CO                                                               MeSCH.sub.2 O(CH.sub.2).sub.9 CO                          328                                                                              MeSCH.sub.2 O(CH.sub.2).sub.11 CO                                                              MeSCH.sub.2 O(CH.sub.2).sub.11 CO                         329                                                                              MeSCH.sub.2 O(CH.sub.2).sub.15 CO                                                              MeSCH.sub.2 O(CH.sub.2).sub.15 CO                         __________________________________________________________________________

Of the compounds listed above, the following are preferred, that is tosay Compounds No. 13, 15, 17, 19, 21, 23, 25, 28, 31, 34, 36, 38, 64,66, 68, 70, 72, 74, 76, 78, 79, 80, 82, 84, 86, 99, 100, 101, 102, 144,146, 152, 154, 160, 162, 164, 165, 179, 180, 181, 184, 185, 186, 189,190, 191, 198, 199, 200, 205, 206, 207, 210, 211, 212, 215, 216, 217,218, 221, 225, 227, 229, 230, 232, 233, 234, 236, 237, 242, 244, 246,248, 249, 250, 251, 252, 253, 258, 260, 262, 263, 264, 271, 272, 273,284, 286, 288, 289, 290, 291, 292, 323, 324, 325, 326, 327, 328 and 329,of which Compounds No. 13, 15, 17, 19, 21, 23, 25, 28, 31, 34, 36, 38,64, 66, 68, 70, 72, 74, 76, 78, 79, 80, 82, 84, 86, 99, 100, 101, 102,144, 146, 152, 154, 160, 162, 164, 165, 179, 180, 181, 198, 199, 200,205, 206, 207, 210, 211, 212, 216, 217, 218, 227, 229, 230, 232, 233,234, 242, 244, 246, 248, 249, 250, 251, 252, 253, 258, 260, 262, 263,264, 284, 286, 288, 289, 290, 291, 292, 323, 324, 325, 326, 327, 328 and329 are more preferred, and Compounds No. 13, 15, 17, 19, 21, 23, 25,28, 31, 34, 36, 38, 64, 66, 68, 70, 72, 74, 76, 78, 79, 80, 82, 284,286, 288, 289, 290, 291, 292, 323, 324, 325, 327, 328 and 329 are stillmore preferred. The most preferred individual compounds are CompoundsNo.:

15. 14,16-diundecanoylradicicol;

17. 14,16-dilauroylradicicol;

19. 14,16-ditridecanoylradicicol;

21. 14,16-dimyristoylradicicol;

23. 14,16-dipentadecanoylradicicol;

25. 14,16-dipalmitoylradicicol;

28. 14,16-diheptadecanoylradicicol;

31. 14,16-distearoylradicicol;

70. 14,16-dipalmitoleoylradicicol;

72. 14,16-dioleoylradicicol, and its isomeric 14,16-dielaidoylradicicol;

76. 14,16-dilinolenoylradicicol;

84. 14,16-di(16-hydroxypalmitoyl)radicicol;

146. 14,16-di(16-aminopalmitoyl)radicicol;

234. 14,16-di(16-carboxytridecanoyl)radicicol;

260. 14,16-di(16-mercaptopalmitoyl)radicicol;

288. 16-palmitoyl-14-stearoylradicicol;

323. 14-elaidoyl-16-palmitoylradicicol; and

325. 16-palmitoyl-14-(10-undecenoyl)radicicol.

The compounds of the present invention may be prepared by a variety ofmethods well known for preparing acylated compounds from thecorresponding hydroxy compound. For example, compounds of formula (I)may be prepared by reacting a compound of formula (II): ##STR2## [inwhich either both of R⁸ and R⁹ represents a hydrogen atom or one of R⁸and R⁹ represents a hydrogen atom and the other represents ahydroxy-protecting group, which may be one of the groups defined for R¹and R² (other than a hydrogen atom) or any of the hydroxy-protectinggroups exemplified above] with a compound of formula (III):

    R.sup.3 --COOH                                             (III)

(in which R³ is as defined above) or with a reactive derivative thereof,and, if required, removing any protecting group, to give said compoundof formula (I).

Radicicol itself is the compound of formula (II) in which both R⁸ and R⁹represent hydrogen atoms.

The reaction of the compound of formula (II) with a carboxylic acid offormula (III):

    R.sup.3 COOH                                               (III)

(in which R³ is as defined above) or with a reactive derivative thereofcan be conducted using any acylation reaction known this field.

If a carboxylic acid of formula (III) is used in the form of the freeacid, the reaction is preferably effected in the presence of a suitablecondensation agent, for example 1,1'-oxalyldiimidazole. 2,2'-dipyridyldisulfide, N,N'-dicyclohexylcarbodiimide (DCC), N,N'-disuccinimidylcarbonate, N,N'-bis(2-oxo-3-oxazolidinyl)phosphinic chloride,N,N'-carbodiimidazole, N,N'-disuccinimidyl oxalate (DSO),N,N'-diphthalimide oxalate (DPO),N,N'-bis(norbornenylsuccinimidyl)oxalate (BBTO),1,1'-bis(benzotriazolyl)oxalate (BBTO),1,1'-bis(6-chlorobenzotriazolyl)oxalate (BCTO) or1,1'-bis(6-trifluoromethylbenzotriazolyl)oxalate (BTBO).

When a condensation agent is employed, the reaction is preferablyconducted in the presence of an inert solvent. There is no particularrestriction on the nature of the solvent to be employed, provided thatit has no adverse effect on the reaction or on the reagents involved andthat it can dissolve the reagents, at least to some extent. Examples ofsuitable solvents include: aliphatic hydrocarbons, such as hexane,heptane, ligroin and petroleum ether; aromatic hydrocarbons, such asbenzene, toluene and xylene; halogenated hydrocarbons, especiallyaromatic and aliphatic hydrocarbons, such as methylene chloride,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and thedichlorobenzenes; esters, such as ethyl formate, ethyl acetate, propylacetate, butyl acetate and diethyl carbonate; ethers, such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane anddiethyleneglycol dimethyl ether; ketones, such as acetone, methyl ethylketone, methyl isobutyl ketone, isophorone and cyclohexanone; nitrocompounds, which may be nitroalkanes or nitroaranes, such as nitroethaneand nitrobenzene; nitriles, such as acetonitrile and isobutyronitrile;amides, which may be fatty acid amides, such as formamide,dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide;and sulfoxides, such as dimethyl sulfoxide and sulfolane.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from -10° C. to 130° C.

If R¹ and R² are the same in the compound of formula (I), the compoundof the present invention can be obtained by reaction of a compound offormula (II) as defined above with 2 and more equivalents of acarboxylic acid and a condensation agent or of a reactive derivative ofthe carboxylic acid. If a compound in which one of R¹ and R² representsa hydrogen atom is desired, it can be obtained by using less than 2equivalents, preferably from 1 to 1.5 equivalents, of the carboxylicacid and a condensation agent or of a reactive derivative of thecarboxylic acid.

If R¹ and R² both represent acyl groups which are different from eachother in the compound of formula (I), the desired compound can beobtained by reaction of a compound of formula (II) in which one of R⁸and R⁹ represents a hydrogen atom with 1 or more equivalents of thecarboxylic acid and a condensation agent or of a reactive derivative ofthe carboxylic acid.

Examples of reactive derivatives of the carboxylic acid of formula (III)include: acid halides, such as the acid chloride and the acid bromide;and acid anhydrides.

When an acid halide is employed, the reaction is preferably conducted inan inert organic solvent in the presence of an acid binding agent. Thereis no particular restriction on the nature of the solvent to beemployed, provided that it has no adverse effect on the reaction or onthe reagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include: aromatichydrocarbons, such as benzene, toluene and xylene; halogenatedhydrocarbons, especially halogenated aliphatic hydrocarbons, such aschloroform, methylene chloride and trichloroethane; ethers, such asdiethyl ether, tetrahydrofuran and dioxane; aliphatic dialkylamides,which may be fatty acid amides, such as dimethylformamide anddimethylacetamide; nitriles, such as acetonitrile; ketones, such asacetone; dimethyl sulfoxide; and pyridine. The acid binding agent may beany such compound which binds to an acid and does not interfere with thereaction, and examples include: alkali metal hydroxides, such as sodiumhydroxide and potassium hydroxide; alkali metal carbonates, such assodium carbonate and potassium carbonate; and organic bases, such astriethylamine, pyridine, 4-dimethylaminopyridine and 1-methylimidazole.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from -10° C. to 130° C.

When an acid anhydride is employed, the reaction is preferably carriedout in the presence of an inert organic solvent, or in the absence of aninert organic solvent by using an excess of the acid anhydride. There isno particular restriction on the nature of the solvent which may beemployed, provided that it has no adverse effect on the reaction or onthe reagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include: aromatichydrocarbons, such as benzene, toluene and xylene; and ethers, such asdioxane, tetrahydrofuran, diethyleneglycol dimethyl ether.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from room temperature to 160° C.

The desired compound thus obtained can be collected, separated andpurified by any suitable techniques. For example, one suitable recoveryprocedure comprises: pouring the reaction solution into water; extractedthe resulting mixture with a water-immiscible solvent, such as benzene,ether or ethyl acetate; and finally removing the solvent e.g. bydistillation to obtain the desired compound. The desired compound may,if necessary, be further purified by various methods, including:adsorption chromalography or ion exchange chromalography using variouscarriers, such as active carbon or silica gel; by gel filtration byusing a Sephadex (trade mark) column; or by recrystallization from anether (e.g. diethyl ether), ethyl acetate or chloroform.

When the compound of formula (II) contains a protecting group, thedesired compound of formula (I) can be obtained by its removal, ifnecessary.

The removal of protecting group is required, the reaction employed will,as is well known in the art, vary depending upon the nature of theprotecting group, and may be carried out using conventional proceduresknown in the technology of this field, for example as follows.

If a silyl group is employed as the hydroxy-protecting group, it cangenerally be removed by treatment with a compound capable of formingfluorine anions, such as tetrabutylammonium fluoride. The reaction ispreferably carried out in the presence of a solvent. There is noparticular restriction on the nature of the solvent to be employed,provided that it has no adverse effect on the reaction or on thereagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include ethers, such astetrahydrofuran and dioxane.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of about room temperature. The time required for thereaction may also vary widely, depending on many factors, notably thereaction temperature and the nature of the reagents. However, providedthat the reaction is effected under the preferred conditions outlinedabove, a period of from 10 to 18 hours will usually suffice.

If the hydroxy group is protected by an aralkyl or aralkyloxycarbonylgroup, it can be removed by contact with a reducing agent. The removalis preferably performed by means of a catalytic reduction, which maytake place at room temperature, by using a catalyst, such aspalladium-carbon, platinum or Raney nickel. The reaction is normally andpreferably carried out in the presence of a solvent. There is noparticular restriction on the nature of the solvent to be employed,provided that it has no adverse effect on the reaction or on thereagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include: alcohols, such asmethanol and ethanol; ethers, such as tetrahydrofuran and dioxane;aliphatic acids, such as acetic acid; and a mixtures of any one or moreof these organic solvents with water.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to room temperature. The time required for thereaction may also vary widely, depending on many factors, notably thereaction temperature and the nature of the reagents. However, providedthat the reaction is effected under the preferred conditions outlinedabove, a period of from 5 minutes to 12 hours will usually suffice.

Such groups can be also removed by treating the compound with lithium orsodium in a liquid ammonia or in an alcohol, such as methanol or ethanolat a relatively low temperature, for example from -78° C. to -20° C.

Such groups can also be removed by using aluminum chloride-sodium iodideor an alkylsilyl halide, such as trimethylsilyl iodide. The reaction isnormally and preferably carried out in the presence of a solvent. Thereis no particular restriction on the nature of the solvent to beemployed, provided that it has no adverse effect on the reaction or onthe reagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include: nitriles, such asacetonitile; halogenated hydrocarbons, especially halogenated aliphatichydrocarbons, such as methylene chloride and chloroform; and mixtures ofany two or more of these solvents.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 50° C.

When the reaction substrate contains a sulfur atom, aluminumchloride-sodium iodide is preferably employed.

If the hydroxy-protecting group is an aliphatic acyl, aromatic acyl oralkoxycarbonyl group, it can be removed by treatment with a base in thepresence of a solvent. The base employed is not particularly limitedprovided that it does not affect other parts of the compounds. Thereaction is preferably performed using one of the following bases: metalalcoholates, such as sodium methoxide; aqueous ammonia; alkali metalcarbonates, such as sodium carbonate and potassium carbonate; alkalimetal hydroxides, such as sodium hydroxide and potassium hydroxide; andconcentrated ammonia-methanol. There is no particular restriction on thenature of the solvent to be employed, provided that it has no adverseeffect on the reaction or on the reagents involved and that it candissolve the reagents, at least to some extent, and any solvent commonlyused for hydrolysis reactions can equally be used here. Examples ofsuitable solvents include: alcohols, such as methanol, ethanol andpropanol; ethers, such as tetrahydrofuran and dioxane; and mixtures ofany one or more of these organic solvents with water.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 150° C. in order to inhibit any sidereaction. The time required for the reaction may also vary widely,depending on many factors, notably the reaction temperature and thenature of the reagents. However, provided that the reaction is effectedunder the preferred conditions outlined above, a period of from 1 to 10hours will usually suffice.

When the hydroxy-protecting group is an alkoxymethyl, tetrahydropyranyl,tetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydrothiofuranyl orsubstituted ethyl group, it can generally be removed by treatment withan acid in a solvent. Examples of suitable acids include: hydrochloricacid, acetic acid-sulfuric acid, p-toluenesulfonic acid and acetic acid.A strong acidic cation exchange resin, such as Dowex 50W can be employedinstead. There is no particular restriction on the nature of the solventto be employed, provided that it has no adverse effect on the reactionor on the reagents involved and that it can dissolve the reagents, atleast to some extent. Examples of suitable solvents include: alcohols,such as methanol and ethanol; ethers, such as tetrahydrofuran anddioxane; and mixtures of any one or more of these solvents with water.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 50° C. The time required for the reactionmay also vary widely, depending on many factors, notably the reactiontemperature and the nature of the reagents. However, provided that thereaction is effected under the preferred conditions outlined above, aperiod of from 10 minutes to 18 hours will usually suffice.

When the hydroxy-protecting group is an alkenyloxycarbonyl group, it canbe removed by treatment with a base under similar conditions to thosementioned above for the case when the hydroxy-protecting group is analiphatic acyl, aromatic acyl or alkoxycarbonyl group.

When the hydroxy-protecting group is an aryloxycarbonyl group, it caneasily be removed using palladium together with triphenylphosphine ornickeltetracarbonyl with few side reactions.

When the amino-protecting group is a trialkylsilyl group, it can beremoved by treating the compound with a compound as capable of formingfluorine anions, for example tetrabutylammonium fluoride. The reactionis normally and preferably effected in the presence of a solvent. Thereis no particular restriction on the nature of the solvent to beemployed, provided that it has no adverse effect on the reaction or onthe reagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include ethers, such astetrahydrofuran and dioxane. The reaction can take place over a widerange of temperatures, and the precise reaction temperature is notcritical to the invention. In general, we find it convenient to carryout the reaction at a temperature of about room temperature. The timerequired for the reaction may also vary widely, depending on manyfactors, notably the reaction temperature and the nature of thereagents. However, provided that the reaction is effected under thepreferred conditions outlined above, a period of from 10 to 18 hourswill usually suffice.

When the amino-protecting group is an aliphatic acyl, aromatic acyl oralkoxycarbonyl group or a substituted methylene group capable of forminga Schiff base, it can be removed by treatment with an acid or a base inthe presence of an aqueous solvent. Suitable acids include hydrochloricacid, sulfuric acid, phosphoric acid and hydrobromic acid. Suitablebases may be selected from any commonly known bases, provided that theydo not affect the other parts of the compound, and examples include:alkali metal carbonates, such as sodium carbonate and potassiumcarbonate; alkali metal hydroxides, such as sodium hydroxide andpotassium hydroxide; and concentrated ammonia-methanol. There is noparticular restriction on the nature of the solvent to be employed,provided that it has no adverse effect on the reaction or on thereagents involved and that it can dissolve the reagents, at least tosome extent, and any solvent commonly used for hydrolysis reactions mayequally be employed here. Examples of suitable solvents include: water;mixtures of one or more alcohols, such as methanol, ethanol or propanol,with water; and mixtures of one or more ethers, such as tetrahydrofuranor dioxane, with water. The reaction can take place over a wide range oftemperatures, and the precise reaction temperature is not critical tothe invention. In general, we find it convenient to carry out thereaction at a temperature of from 0° C. to 150° C., in order to inhibitany side reaction. The time required for the reaction may also varywidely, depending on many factors, notably the reaction temperature andthe nature of the reagents. However, provided that the reaction iseffected under the preferred conditions outlined above, a period of from1 to 10 hours will usually suffice.

When the amino-protecting group is an aralkyl or aralkyloxycarbonylgroup, it can preferably be removed by catalytic reduction at roomtemperature using, for example, platinum or palladium-on-carbon; or byusing an oxidizing agent.

For the reductive removal, there is no particular restriction on thenature of the solvent to be employed, provided that it has no adverseeffect on the reaction or on the reagents involved and that it candissolve the reagents, at least to some extent. Examples of suitablesolvents include: alcohols, such as methanol, ethanol and isopropanol;ethers, such as diethyl ether, tetrahydrofuran and dioxane; aromatichydrocarbons, such as toluene, benzene and xylene; aliphatichydrocarbons, such as hexane and cyclohexane; esters, such as ethylacetate and propyl acetate; aliphatic acids, such as acetic acid; andmixtures of any one or more of these solvents with water.

Preferred catalysts which may be used in this reaction are notparticularly limited, provided that they are capable of use in catalyticreduction; and examples include: palladium-on-carbon, Raney nickel,platinum oxide, platinum black, rhodium-on-aluminum oxide,triphenylphosphine-on-rhodium chloride and palladium-on-barium sulfate.

Although there is no particular restriction on the pressure employed,the reaction is usually carried out at from 1 to 10 atmospheres.

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention, althoughthe preferred temperature will vary, as is known in the art, dependingupon the starting materials and the catalyst. In general, we find itconvenient to carry out the reaction at a temperature of from 0° C. to100° C. The time required for the reaction may also vary widely,depending on many factors, notably the reaction temperature and thenature of the reagents. However, provided that the reaction is effectedunder the preferred conditions outlined above, a period of from 5minutes to 24 hours will usually suffice.

For the oxidative removal, there is no particular restriction on thenature of the solvent to be employed, provided that it has no adverseeffect on the reaction or on the reagents involved and that it candissolve the reagents, at least to some extent. Examples of suitablesolvents include: aqueous organic solvents; preferred organic solventswhich may be used include: ketones, such as acetone; halogenatedhydrocarbons, especially halogenated aliphatic hydrocarbons, such asmethylene chloride, chloroform and carbon tetrachloride; nitriles, suchas acetonitrile; ethers, such as diethyl ether, tetrahydrofuran anddioxane; amides, which may be fatty acid amides, such asdimethylformamide, dimethylacetamide and hexamethylphosphorotriamide;and sulfoxides, such as dimethyl sulfoxide.

There is no particular restriction on the nature of the oxidizing agentemployed, provided that it is capable of use for oxidation, andpreferred examples include: potassium persulfate, sodium persulfate,ammonium cerium nitrate (CAN) and2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ).

The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 150° C., depending on the startingmaterials and the catalyst employed. The time required for the reactionmay also vary widely, depending on many factors, notably the reactiontemperature and the nature of the reagents. However, provided that thereaction is effected under the preferred conditions outlined above, aperiod of from 10 minutes to 24 hours will usually suffice.

When the amino-protecting group is an alkenyloxycarbonyl group, it canbe removed by treatment with a base under similar conditions to thoseemployed when the protecting group is an aliphatic acyl, aromatic acylor lower alkoxycarbonyl group. In particular, when the amino-protectinggroup is an allyloxycarbonyl group, it can be removed conveniently andwith few side reaction by using palladium and triphenylphosphine ornickeltetracarbonyl.

When the mercapto-protecting group is an aralkyl or aralkyloxycarbonylgroup, it can generally be removed by contact with a reducing agent. Forexample, the removal may be performed by catalytic reduction at roomtemperature using palladium-on-carbon, platinum or Raney nickel as thecatalyst. The reaction is conducted in the presence of a solvent. Thereis no particular restriction on the nature of the solvent to beemployed, provided that it has no adverse effect on the reaction or onthe reagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include: alcohols, such asmethanol and ethanol; ethers, such as tetrahydrofuran and dioxane;aliphatic acids, such as acetic acid; and mixtures of any one or more ofthese solvents with water. The reaction can take place over a wide rangeof temperatures, and the precise reaction temperature is not critical tothe invention. In general, we find it convenient to carry out thereaction at a temperature of from 0° C. to room temperature, dependingon the starting materials and the reducing agent employed. The timerequired for the reaction may also vary widely, depending on manyfactors, notably the reaction temperature and the nature of thereagents. However, provided that the reaction is effected under thepreferred conditions outlined above, a period of from 5 minutes to 12hours will usually suffice.

Such groups can alternatively be removed by treatment with lithium orsodium in liquid ammonia or an alcohol, such as methanol or ethanol, ata relatively low temperature, e.g. from -78° C. to -20° C.

Alternatively, such groups can be removed by using aluminumchloride-sodium iodide or an alkylsilyl halide, such as trimethylsilyliodide. The reaction is carried out in the presence of a solvent. Thereis no particular restriction on the nature of the solvent to beemployed, provided that it has no adverse effect on the reaction or onthe reagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include: nitriles, such asacetonitrile; halogenated hydrocarbons, especially halogenated aliphatichydrocarbons, such as methylene chloride and chloroform; and mixtures ofany two or more of these solvents. The reaction can take place over awide range of temperatures, and the precise reaction temperature is notcritical to the invention. In general, we find it convenient to carryout the reaction at a temperature of from 0° C. to 50° C., depending onthe starting materials. The time required for the reaction may also varywidely, depending on many factors, notably the reaction temperature andthe nature of the reagents.

When the mercapto-protecting group is an alkoxycarbonyl group, such as at-butoxycarbonyl group or an arylmethyl group, it can be removed bytreatment with an acid in the presence of a solvent. Preferred acidsinclude, for example, trifluoroacetic acid and acetic acid-hydrobromicacid. There is no particular restriction on the nature of the solvent tobe employed, provided that it has no adverse effect on the reaction oron the reagents involved and that it can dissolve the reagents, at leastto some extent. Examples of suitable solvents include: alcohols, such asmethanol and ethanol; ethers, such as tetrahydrofuran and dioxane; andmixtures of any one or more of these solvents with water. The reactioncan take place over a wide range of temperatures, and the precisereaction temperature is not critical to the invention. In general, wefind it convenient to carry out the reaction at a temperature of from 0°C. to 50° C., depending on the starting materials and the acid employed.The time required for the reaction may also vary widely, depending onmany factors, notably the reaction temperature and the nature of thereagents. However, provided that the reaction is effected under thepreferred conditions outlined above, a period of from 10 minutes to 18hours will usually suffice.

When the mercapto-protecting group is an aliphatic acyl, aromatic acylor alkoxycarbonyl group, it can be removed by treatment with a base inthe presence of a solvent. There is no particular restriction on thenature of the base employed, provided that it does not affect the otherparts of the compound, and examples include: metal alcoholates, such assodium methoxide; aqueous ammonia; alkali metal carbonates, such assodium carbonate and potassium carbonate; alkali metal hydroxides, suchas sodium hydroxide and potassium hydroxide; and concentratedammonia-methanol. There is no particular restriction on the nature ofthe solvent to be employed, provided that it has no adverse effect onthe reaction or on the reagents involved and that it can dissolve thereagents, at least to some extent, and any solvent commonly employed forhydrolysis reactions may equally be employed here. Examples of suitablesolvents include: water; alcohols, such as methanol, ethanol andpropanol; ethers, such as tetrahydrofuran and dioxane; and mixture ofany one or more of these organic solvents with water. The reaction cantake place over a wide range of temperatures, and the precise reactiontemperature is not critical to the invention. In general, we find itconvenient to carry out the reaction at a temperature of from 0° C. to150° C., depending on the starting materials and the base employed, inorder to inhibit any side reaction. The time required for the reactionmay also vary widely, depending on many factors, notably the reactiontemperature and the nature of the reagents. However, provided that thereaction is effected under the preferred conditions outlined above, aperiod of from 1 to 10 hours will usually suffice.

When the mercapto-protecting group is a tetrahydropyranyl group, it cangenerally be removed by treatment with an acid in a solvent. Preferredacids which may be used in this reaction include hydrochloric acid,acetic acid-sulfuric acid, p-toluenesulfonic acid and acetic acid. Astrong acidic cation exchange resins, such as Dowex 50W may be employedinstead. There is no particular restriction on the nature of the solventto be employed, provided that it has no adverse effect on the reactionor on the reagents involved and that it can dissolve the reagents, atleast to some extent. Examples of suitable solvents include: alcohols,such as methanol and ethanol; ethers, such as tetrahydrofuran anddioxane; and mixtures of any one or more of these solvents with water.The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 50° C., depending on the starting materialsand the acid employed. The time required for the reaction may also varywidely, depending on many factors, notably the reaction temperature andthe nature of the reagents. However, provided that the reaction iseffected under the preferred conditions outlined above, a period of from10 minutes to 18 hours will usually suffice.

When the mercapto-protecting group is an alkenyloxycarbonyl group, itcan be removed by treatment with a base under similar conditions tothose employed when the protecting group is an aliphatic acyl, aromaticacyl or alkoxycarbonyl group.

In particular, when the mercapto-protecting group is an allyloxycarbonylgroup, it can be removed conveniently and with few side reactions byusing palladium and triphenylphosphine or nickeltetracarbonyl.

When the mercapto-protecting group is an S-2-pyridinesulfenyl orS-3-nitro-2-pyridinesulfenyl group, it can be removed by reaction with asecondary amine, such as triphenylphosphine, pyrrolidine, piperidine ormorpholine.

When the carboxy-protecting group is a lower alkyl group or an arylgroup, it can be removed by treatment with an acid or a base.

Suitable acids include hydrochloric acid, sulfuric acid, phosphoric acidand hydrobromic acid. Suitable bases do not affect other parts of thecompound, and examples include alkali metal carbonates, such as sodiumcarbonate and potassium carbonate, alkali metal hydroxides, such assodium hydroxide and potassium hydroxide, and concentratedammonia-methanol.

There is no particular restriction on the nature of the solvent to beemployed, provided that it has no adverse effect on the reaction or onthe reagents involved and that it can dissolve the reagents, at least tosome extent, and any solvent commonly used for hydrolysis reactions mayequally be used here. Examples of suitable solvents include: water; andmixtures of water with an alcohol, such as methanol, ethanol orpropanol, or with an ether, such as tetrahydrofuran or dioxane. Thereaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 150° C., depending on the startingmaterials and the base employed, in order to inhibit any side reaction.The time required for the reaction may also vary widely, depending onmany factors, notably the reaction temperature and the nature of thereagents. However, provided that the reaction is effected under thepreferred conditions outlined above, a period of from 1 to 10 hours willusually suffice.

When the carboxy-protecting group is a di-aryl-substituted methyl group,such as a diphenylmethyl group, it can generally be removed under acidicconditions. The reaction is normally and preferably effected in thepresence of a solvent. There is no particular restriction on the natureof the solvent to be employed, provided that it has no adverse effect onthe reaction or on the reagents involved and that it can dissolve thereagents, at least to some extent. Examples of suitable solvents includearomatic hydrocarbons, such as anisole. Suitable acids includefluoro-organic acids, such as trifluoroacetic acid. The reaction cantake place over a wide range of temperatures, and the precise reactiontemperature is not critical to the invention. In general, we find itconvenient to carry out the reaction at a temperature of about roomtemperature, depending on the starting materials. The time required forthe reaction may also vary widely, depending on many factors, notablythe reaction temperature and the nature of the reagents. However,provided that the reaction is effected under the preferred conditionsoutlined above, a period of from 30 minutes to 10 hours will usuallysuffice.

When the carboxy-protecting group is an aralkyl or halogenated loweralkyl group, it can be removed in general by contact with a reducingagent.

When the carboxy-protecting group is a halogenated lower alkyl group,zinc-acetic acid is preferably employed as the reducing agent. When thecarboxy-protecting group is an aralkyl group, it can be removed bycatalytic reduction by using palladium-carbon or platinum as thecatalyst, or by using an alkali metal sulfides, such as potassiumsulfide or sodium sulfide.

These reactions may be conducted in the presence of a solvent. There isno particular restriction on the nature of the solvent to be employed,provided that it has no adverse effect on the reaction or on thereagents involved and that it can dissolve the reagents, at least tosome extent. Examples of suitable solvents include: alcohols, such asmethanol and ethanol; ethers, such as tetrahydrofuran and dioxane;aliphatic acids, such as acetic acid; and mixtures of any one or more ofthese solvents with water. The reaction can take place over a wide rangeof temperatures, and the precise reaction temperature is not critical tothe invention. In general, we find it convenient to carry out thereaction at a temperature of from 0° C. to near room temperature,depending on the starting materials and the reducing agent employed. Thetime required for the reaction may also vary widely, depending on manyfactors, notably the reaction temperature and the nature of thereagents. However, provided that the reaction is effected under thepreferred conditions outlined above, a period of from 5 minutes to 12hours will usually suffice.

When the carboxy-protecting group is an alkoxymethyl group, it cangenerally be removed by treatment with an acid. Preferred acids includehydrochloric acid, acetic acid-sulfuric acid and p-toluenesulfonicacid-acetic acid. The reaction is conducted in the presence of asolvent. There is no particular restriction on the nature of the solventto be employed, provided that it has no adverse effect on the reactionor on the reagents involved and that it can dissolve the reagents, atleast to some extent. Examples of suitable solvents include: alcohols,such as methanol and ethanol; ethers, such as tetrahydrofuran anddioxane; and mixtures of any one or more of these solvents with water.The reaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 50° C., depending on the starting materialsand the acid employed. The time required for the reaction may also varywidely, depending on many factors, notably the reaction temperature andthe nature of the reagents. However, provided that the reaction iseffected under the preferred conditions outlined above, a period of from10 minutes to 18 hours will usually suffice.

In addition, where the compound thus obtained is a carboxylic acidcompound, if desired, its corresponding alkali metal salt can beprepared by various conventional procedures, for example as follows: Thecarboxylic acid compound is dissolved in a mixed solvent of water with awater-immiscible organic solvent, such as ethyl acetate, then an aqueoussolution of an alkali metal carbonate and an alkali metal bicarbonates,such as sodium bicarbonate and potassium carbonate, is added to thesolution, preferably at from 0° C. to room temperature; the pH of thesolution is then adjusted to a value of near 7, and the resultingseparated precipitate is collected by filtration.

Furthermore, the salt or the carboxylic acid compound can be convertedto its corresponding ester in which the carboxylic acid is protected bya protecting group which can easily be hydrolyzed in vivo by theprocedures below: The salt or the acid is dissolved in an ether, such astetrahydrofuran, or a polar solvent, such as N,N-dimethylformamide,dimethyl sulfoxide, hexamethylphosphorotriamide or triethylphosphate,and allowed to react with two equivalents of an organic base, such astriethylamine or dicyclohexylamine, an alkali metal hydride, such assodium hydride, or an alkali metal carbonate or bicarbonate, such assodium bicarbonate, sodium carbonate or potassium carbonate, to prepareits salt; and then the salt is allowed to react with an aliphaticacyloxymethyl halide, such as acetoxymethyl chloride orpropionyloxymethyl bromide, a 1-(lower alkoxy)carbonyloxyethyl halide,such as 1-methoxycarbonyloxyethyl chloride or 1-ethoxycarbonyloxyethyliodide, a phthalidyl halide, or a(2-oxo-5-methyl-1,3-dioxoren-4-yl)methyl halide. There is no particularrestriction on the nature of the solvent to be employed, provided thatit has no adverse effect on the reaction or on the reagents involved andthat it can dissolve the reagents, at least to some extent. Examples ofsuitable solvents include any of the polar solvents mentioned above. Thereaction can take place over a wide range of temperatures, and theprecise reaction temperature is not critical to the invention. Ingeneral, we find it convenient to carry out the reaction at atemperature of from 0° C. to 100° C., depending on the startingmaterials, solvent and reagents employed. The time required for thereaction may also vary widely, depending on many factors, notably thereaction temperature and the nature of the reagents. However, providedthat the reaction is effected under the preferred conditions outlinedabove, a period of from 0.5 to 10 hours will usually suffice, y bepreferably employed.

Many of the radicicol derivatives of the present invention show a strongantitumor effect against transplanted M5076 cells in mice, and aretherefore expected to demonstrate activity against solid type tumors ingeneral.

Accordingly, the radicicol derivatives of the present invention can beused in warm-blooded animals, including humans, as an anti-tumor agentagainst these kinds of tumoral diseases. The compounds may beadministered by any convenient route, for example by parenteraladministration methods, such as intravenous injection, subcutaneousinjection, intramuscular injection or by suppositories; or oraladministration by using, for example, capsules, powders or granules.

The dosage to an adult human may vary depending on the nature of thedisease, the route of administration and the administration frequencyand period. However, a daily dosage of from 1 to 100 mg in a single doseor in divided doses may be given.

The radicicol derivative of the present invention may be administered incombination with other antitumor agents, for example, nitrosourea agentssuch as ACNU or BCNU, cisplatin, 5-FU, Daunomycin, adriamycin, mitomycinC and etoposide. In addition, preparations of the radicicol derivativecan be provided for administration according to any conventional method.Therefore, the present invention covers any pharmaceutical preparationsand compositions containing the radicicol derivatives of the presentinvention. The form will, of course, vary depending upon the route ofadministration.

For example, compositions for injection can be provided in the form ofampoules, each containing a unit dose amount, or in the form of acontainer containing multiple doses. The composition may sometimescontain additives such as emulsifiers, stabilizers and/or dispersants,and may often be in the form of a powder which is intended to bedissolved by the pharmacist in a suitable solvent, such as apyrogen-free sterilized aqueous solvent, just before use. Such apreparation can be prepared, for example, as follows: The radicicolderivative is dissolved in acetone, and the acetone solution is pouredinto vials, water is added, and then the mixture is lyophilized. On theother hand, compositions for oral administration can be provided bymeans of capsules, powders, granules or syrups each containing asuitable amount of one or more of the radicicol derivatives of thepresent invention.

BIOLOGICAL ACTIVITY

The test animals used were female mice, 8 weeks old, of the BDF₁ strain,weighing 20-25 g. The mice were purchased from Charles River Japan Inc.,Kanagawa, Japan. The mice were divided into experimental groups, eachgroup containing 6 mice, and all mice within each group were treatedidentically. Each mouse was inoculated subcutaneouly with 1×10⁶ viablecells (the number of cells was measured by a dye exclusion method undermicroscopy) of the mouse fibrosarcoma M5076.

The test compounds (80 mg) listed in the following Table, exceptradicicol, were dissolved in 0.2 ml of N,N-dimethylacetamide (DMA) andto the solution was added 0.2 ml of 40° C.-warmed HCO60 (polyoxyethylenehydrogenated caster oil 60). Immediately thereafter 3.6 ml of 40°C.-warmed physiological saline was added to form a colloidal solution ora suspension. The final concentration of DMA and HCO60 was 5% v/v, each.Radicicol was dissolved in 0.25 mg/ml of DMA and the solution wasdispersed slowly into 3.75 ml of 10% Emulphor(trade mark)-physiologicalsaline stirred well with a stirring rod. The final concentration of DMAwas 6.25%. The solution was administered intravenously (in the case of asuspension it was administered intraperitoneally) on the first, fifthand ninth days following inoculation of the fibrosarcoma cells. Theperiod for which the mice survived and the % inhibition of tumor growthwere determined. A control group was treated identically, except that noactive compound was administered.

The anti-tumor effect is shown in the following Table as the increase inlife span [ILS (%)] and the growth inhibition [GI (%)], calculated fromthe following equations [R. I. Geran et al., Cancer Chemother. Rept., 3(1972)]:

    ILS(%)+(Dt/Dc-1)×100

where

Dt=median survival time (days) of mice in the treated group; and

Dc=median survival time (days) of mice in the control group.

In this experiment, Dc was 40-47 days.

    GI(%)=(1-TDt/TDC)×100

where

TDt=average value of tumor sizes on the fourteenth day in the treatedgroup; and

TDc=average value of tumor sizes on the fourteenth day in the controlgroup tumor size=(tumor length+tumor width )/2.

The compounds of the invention are identified in the following Table bythe numbers assigned to them in the foregoing list.

                  TABLE 2                                                         ______________________________________                                                                    growth                                            Cpd No.  dose (mg/kg)                                                                            route    Inhibition (%)                                                                         ILS (%)                                  ______________________________________                                        17       200       iv       89       24                                       19       200       iv       89        9                                       21       200       iv       91       35                                       23       200       iv       95       35                                       25       200       iv       100      43                                       28       200       iv       95       27                                       31       200       ip       66       -4                                       70       200       iv       65       31                                       72(cis)  200       iv       80        4                                       72(trans)                                                                              200       iv       86        9                                       76       200       iv       74       11                                       radicicol                                                                              150       iv        5       -29                                      ______________________________________                                    

As is shown in the above Table, all of the compounds tested exhibitedhigher anti-tumor activitives than radicicol in the solid type tumormodel (M5076 fibrosarcome sc implanted) in terms of both of tumor growthinhibition and increase in life span.

The invention is further illustrated by the following non-limitingExamples.

EXAMPLE 1 14,16-Dipalmitoylradicicol

1.6 g of radicicol was dissolved in 37 ml of dry benzene, and thesolution was placed on an ice bath. While the solution was still on theice bath, 2.2 ml of pyridine and a catalytic amount ofdimethylaminopyridine were added to it, after which 20 ml of benzenecontaining 1.32 g of palmitoyl chloride was added dropwise. The reactionsolution was then stirred for 1 hour on an ice bath, and ice water wasadded; it was then extracted with ethyl acetate. The organic layer waswashed with an aqueous solution of sodium bicarbonate, with water andwith a saturated solution of sodium chloride, in that order, after whichit was dried over anhydrous magnesium sulfate. The magnesium sulfate wasremoved by filtration, and the solvent was then removed from thefiltrate by distillation under reduced pressure. 2.70 g of an oilyresidue were thus obtained, and this was subjected to silica gel columnchromatography using a 1:1 by volume mixture of hexane and ethyl acetateas the eluent, to obtain a crystalline substance having an Rf value of0.64 (developing solvent, hexane:ethyl acetate=3:1 by volume).Recrystallization of this from hexane afforded 1.47 g of the titlecompound.

Nuclear Magnetic Resonance Spectrum (CDCl₃) δ ppm: 0.88 (6H, triplet,J=6.3 Hz); 1.21-1.42 (5OH, multiplet); 1.53 (3H, doublet, J=4.8 Hz);1.63-1.79 (3H, multiplet); 2.37-2.45 (1H, multiplet); 2.49 (2H, triplet,J=6.8 Hz); 2.58 (2H, triplet, J=7.3 Hz); 2.99-3.02 (1H, multiplet); 3.52(1H, multiplet); 3.91, 4.03 (2H, AB-quartet, J=16.1 Hz); 5.39-5.41 (1H,multiplet); 5.78 (1H, doublet of doublets, J=3.9 & 10.7 Hz); 6.06 (1H,doublet, J=16.1 Hz); 6.14 (1H, doublet of doublets, J=10.7 & 10.3 Hz);7.01 (1H, singlet); 7.52 (1H, doublet of doublets, J=16.0 & 10.3 Hz).

Infrared Absorption Spectrum (Nujol--trade mark) ν_(max) cm⁻¹ : 1759,1722.

EXAMPLE 2 14-Palmitoylradicicol

After the silica gel column chromatography of the mixture obtained asdescribed in Example 1, 866 mg of the title compound having an Rf valueof 0.31 (developing solvent, hexane:ethyl acetate=1:1 by volume) wereobtained. Recrystallization from hexane afforded 731 mg of the titlecompound as white crystals.

Nuclear Magnetic Resonance Spectrum (CDCl₃) δ ppm: 0.88 (3H, triplet,J=6.3 Hz); 1.20-1.50 (24H, multiplet); 1.54 (3H, doublet, J=6.3 Hz);1.72-1.80 (2H, multiplet); 1.85-1.96 (1H, multiplet); 2.34-2.42 (1H,multiplet); 2.59 (2H, triplet, J=7.3 Hz); 2.92-2.97 (1H, multiplet);3.17 (1H, multiplet); 3.97, 4.69 (2H, AB-quartet, J=16.0 Hz); 5.53-5.58(1H, multiplet); 5.83 (1H, doublet of doublets, J=10.7 & 3.0 Hz); 6.10(1H, doublet, J=16.1 Hz); 6.14 (1H, doublet of doublets, J=10.7 & 9.2Hz); 6.84 (1H, singlet); 7.42 (1H, doublet of doublets, J=17.0 & 9.2Hz); 10.78 (1H, singlet).

Infrared Absorption Spectrum (Nujol) ν_(max) cm⁻¹ : 1772, 1717.

Elemental analysis: Calculated for C₃₄ H₄₇ O₇ Cl: C, 67.70%; H, 7.85%;Cl, 5.88%. Found: C, 67.43%; H, 7.77%; Cl, 6.15%.

EXAMPLE 3 14,16-Di(octanoyl)radicicol

A procedure similar to that described in Example 1 was repeated, exceptthat a mixture of 320 mg of radicicol, 7.4 ml of dry benzene, 880 μl ofpyridine, a catalytic amount of dimethylaminopyridine and 338 mg (2.4times the equimolar amount) of octanoyl chloride were used, to give1.514 mg (yield 95%) of the title compound as an oily substance.

Nuclear Magnetic Resonance Spectrum (CDCl₃) δ ppm: 0.84-0.96 (6H,multiplet); 1.22-1.45 (17H, multiplet); 1.53 (3H, doublet, J=6.8 Hz);1.51-1.62 (1H, multiplet); 1.64-1.80 (4H, multiplet); 2.36-2.44 (1H,multiplet); 2.50 (2H, triplet, J=7.4 Hz); 2.58 (2H, triplet, J=7.3 Hz);2.96-3.04 (1H, multiplet); 3.52 (1H, multiplet); 3.91, 4.03 (2H,AB-quartet, J=16.1 Hz); 5.34-5.45 (1H, multiplet); 5.78 (1H, doublet ofdoublets, J=10.7 & 3.4 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,doublet of doublets, J=10.2 & 10.7 Hz); 7.01 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.0 & 10.2 Hz);

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1765, 1735

EXAMPLE 4 14,16-Di(behenoyl)radicicol

A methylene chloride solution containing 2.24 g of behenoyl chloride wasadded dropwise to a mixed solution of 1.459 g of radicicol, 37 ml of drymethylene chloride, 1.9 ml of pyridine and a catalytic amount ofdimethylaminopyridine on an ice bath. The mixture was then reacted andtreated as described in Example 1, to give a crystalline product havingan Rf value of 0.80 (developing solvent, benzene:ethyl acetate=9:1 byvolume). Recrystallization of this from hexane afforded 1.63 g of thetitle compound.

Nuclear Magnetic Resonance Spectrum (CDCl₃) δ ppm: 0.88 (6H, doublet,J=6.4 Hz); 1.24-1.45 (72H, multiplet); 1.54 (3H, doublet, J=6.8 Hz);1.48-1.81 (5H, multiplet); 2.37-2.46 (1H, multiplet); 2.49 (2H, triplet,J=7.3 Hz); 2.58 (2H, triplet, J=7.3 Hz); 2.99-3.02 (1H, multiplet); 3.52(1H, multiplet); 3.91, 4.03 (2H, AB-quartet, J=16.6 Hz); 5.36-5.45 (1H,multiplet); 5.78 (1H, doublet of doublets, J=11.0 & 3.9 Hz); 6.06 (1H,doublet, J=16.2 Hz); 6.14 (1H, doublet of doublets, J=11.0 & 10.3 Hz);7.01 (1H, singlet); 7.52 (1H, doublet of doublets, J=11.0 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm ⁻¹ : 1770, 1738.

Elemental analysis: Calculated for C₆₂ H₁₀₁ O₈ Cl: C, 73.74%; H, 10.08%;Cl, 3.51%. Found: C, 73.71%; H, 9.84%; Cl, 3.52%.

EXAMPLE 5 14-Behenoylradicicol

After the silica gel column chromatography of the mixture obtained asdescribed in Example 4, a crystalline product having an Rf value of 0.64(developing solvent, benzene:ethyl acetate=9:1 by volume) was obtained.Recrystallization of this from hexane afforded 463 mg of the titlecompound.

Nuclear Magnetic Resonance Spectrum (CDCl₃) δ ppm: 0.85 (3H, triplet,J=7.3 Hz); 1.22-1.45 (37H, multiplet); 1.54 (3H, doublet, J=6.8 Hz);1.72-1.83 (2H, multiplet); 1.85-1.97 (1H, multiplet); 2.33-2.42 (1H,multiplet); 2.53 (2H, triplet, J=7.4 Hz); 2.93-2.97 (1H, multiplet);3.16 (1H, multiplet); 3.96, 4.69 (2H, AB-quartet, J=16.6 Hz); 5.52-5.63(1H, multiplet); 5.83 (1H, doublet of doublets, J=110 & 2.4 Hz); 6.10(1H, doublet, J=16.1 Hz); 6.18 (1H, doublet of doublets, J=16.0 & 11.0Hz); 6.84 (1H, singlet); 7.42 (1H, doublet of doublets, J=16.0 & 9.3Hz); 10.78 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1725.

Elemental analysis: Calculated for C₄₀ H₅₉ O₇ Cl: C, 69.90%; H, 8.65%;Cl, 5.16%. Found: C. 69.87%; H, 8.56%; Cl, 5.18%.

EXAMPLE 6 14,16-Di(stearoyl)radicicol

A procedure similar to that described in Example 4 was repeated, exceptthat a mixed solution containing 1.459 g of radicicol, 37 ml of drymethylene chloride, 1.9 ml of pyridine, a catalytic amount ofdimethylaminopyridine and 1.454 g of stearoyl chloride were reacted andtreated, to give 923 mg of the title compound as crystals.

Nuclear Magnetic Resonance Spectrum (CDCl₃) δ ppm: 0.88 (6H, triplet,J=6.4 Hz); 1.21-1.42 (56H, multiplet); 1.53 (3H, doublet, J=6.8 Hz);1.50-1.62 (1H, multiplet); 1.65-1.80 (4H, multiplet); 2.37-2.46 (1H,multiplet); 2.49 (2H, triplet, J=6.8 Hz); 2.58 (2H, triplet, J=7.3 Hz);2.99-3.05 (1H, multiplet); 3.52 (1H, multiplet); 3.91, 4.63 (2H,AB-quartet, J=16.6 Hz); 5.35-5.46 (1H, multiplet); 5.78 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.2 Hz); 6.14 (1H,doublet of doublets, J=10.7 & 10.3 Hz); 7.01 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.0 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1772, 1740.

Elemental analysis: Calculated for C₅₄ H₈₅ O₈ Cl: C, 72.25%; H, 9.54%;Cl, 3.95%. Found: C, 72.29%; H, 9.30%; Cl, 3.92%.

EXAMPLE 7 14-Stearoylradicicol

After the silica gel column chromatography of the mixture obtained asdescribed in Example 6, a reaction product having an Rf value of 0.35(developing solvent, hexane:ethyl acetate=2:1 by volume) was obtained.Recrystallization of this from hexane afforded 1.09 g of the titlecompound.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (3H,triplet, J=6.4 Hz); 1.19-1.42 (29H, multiplet); 1.54 (3H, doublet, J=6.4Hz); 1.72-1.80 (1H, multiplet); 1.86-1.96 (1H, multiplet); 2.33-2.42(1H, multiplet); 2.59 (2H, triplet, J=7.4 Hz); 2.92-2.97 (1H,multiplet); 3.16 (1H, multiplet); 3.97, 4.69 (2H, AB-quartet, J=16.6Hz); 5.53-5.62 (1H, multiplet); 5.83 (1H, doublet of doublets, J=10.7 &2.4 Hz); 6.10 (1H, doublet, J=16.1 Hz); 6.18 (1H, doublet of doublets,J=10.7 & 9.3 Hz); 6.84 (1H, singlet); 7.42 (1H, doublet of doublets,J=16.0 & 9,3 Hz); 0.78 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1772, 1730

Elemental analysis: Calculated for C₃₆ H₅₁ O₇ Cl: C, 68.50%; H, 8.14%;Cl, 5.62%. Found: C, 68.59%; H, 8.17%; Cl, 5.38%.

EXAMPLE 8 14,16-Di(oleoyl)radicicol

A procedure similar to that described in Example 4 was repeated, exceptthat a mixed solution of 1.641 g of radicicol, 40 ml of dry methylenechloride, 2.14 ml of pyridine, a catalytic amount ofdimethylaminopyridine and 1.49 g of oleoyl chloride were reacted andtreated, to give 1.736 g of the title compound having an Rf value of0.83 (developing solvent, hexane:ethyl acetate=2:1 by volume) as an oilysubstance.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.4 Hz); 1.22-1.42 (42H, multiplet); 1.53 (3H, doublet, J=6.3Hz); 1.63-1.80 (4H, multiplet); 1.93-2.08 (7H, multiplet); 2.36-2.44(1H, multiplet); 2.49 (2H, triplet, J=7.8 Hz); 2.58 (2H, triplet, J=7.3Hz); 2.98-3.03 (1H, multiplet); 3.52 (1H, multiplet); 3.91, 4.03 (2H,AB-quartet, J=16.6 Hz); 5.28-5.46 (5H, multiplet); 5.78 (1H, doublet ofdoublets, J=10.8 & 3.9 Hz); 6.06 (1H, doublet, J=16.2 Hz); 6.14 (1H,doublet of doublets, J=10.8 & 10.3 Hz); 7.01 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.4 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1742.

EXAMPLE 9 14-Oleoylradicicol

After, the silica gel column chromatography of the mixture obtained asdescribed in Example 8, 872 mg of the title compound having an Rf valueof 0.43 (developing solvent, hexane:ethyl acetate, 2:1 by volume) wereobtained as an oily substance.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.87 (3H,triplet, J=6.4 Hz); 1.26-1.46 (22H, multiplet); 1.54 (3H, doublet, J=6.8Hz); 1.72-1.80 (1H, multiplet); 1.86-2.00 (4H, multiplet); 2.33-2.43(1H, multiplet); 2.59 (2H, triplet, J=7.4 Hz); 2.96-2.98 (1H,multiplet); 3.16 (1H, multiplet); 3.98, 4.68 (2H, AB-quartet, J=16.6Hz); 5.32-5.41 (2H, multiplet); 5.52-5.61 (1H, multiplet); 5.83 (1H,doublet of doublets, J=10.0 & 2.9 Hz); 6.10 (1H, doublet, J=16.1 Hz);6.18 (1H, doublet of doublets, J=10.0 & 8.8 Hz); 6.84 (1H, singlet);7.42 (1H, doublet of doublets, J=16.1 & 8.8 Hz); 0.7 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1775, 1732.

EXAMPLE 10 14,16-Di(elaidoyl)radicicol

A procedure similar to that described in Example 4 was repeated, exceptthat a mixed solution containing 1.641 g of radicicol, 40 ml of drymethylene chloride, 2.14 ml of pyridine, a catalytic amount ofdimethylaminopyridine and 1.49 g of elaidoyl chloride was reacted andtreated, to give 1.24 g of the title compound having an Rf value of 0.84(developing solvent, hexane:ethyl acetate=2:1 by volume) as an oilysubstance.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.87 (6H,triplet, J=6.3 Hz); 1.26-1.48 (42H, multiplet); 1.53 (3H, doublet, J=6.3Hz); 1.62-1.79 (4H, multiplet); 1.95-2.05 (7H, multiplet); 2.37-2.42(1H, multiplet); 2.49 (2H, triplet, J=7.3 Hz); 2.58 (2H, triplet, J=7.3Hz); 2.98-3.03 (1H, multiplet); 3.51 (1H, multiplet); 3.91, 4.03 (2H,AB-quartet, J=16.6 Hz); 5.30-5.46 (5H, multiplet); 5.78 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.14 (1H,doublet of doublets, J=10.7 & 10.7 Hz); 7.01 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.0 & 10.7 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1772, 1740.

EXAMPLE 11 14-Elaidoylradicicol

After the silica gel column chromatography of the mixture obtained asdescribed in Example 10, a product having an Rf value of 0.40(developing solvent, hexane:ethyl acetate=2:1 by volume) was obtained.Recrystallization of this product from hexane afforded 1.22 g of thetitle compound as white crystals.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.87 (3H,triplet, J=6.3 Hz); 1.26-1.42 (21H, multiplet); 1.54 (3H, doublet, J=6.3Hz); 1.72-1.80 (2H, multiplet); 1.86-1.96 (5H, multiplet); 2.33-2.43(1H, multiplet); 2.59 (2H, triplet, J=7.3 Hz); 2.92-2.97 (1H,multiplet); 3.16 (1H, multiplet); 3.97, 4.69 (2H, AB-quartet, J=16.6Hz); 5.51-5.59 (1H, multiplet); 5.83 (1H, doublet of doublets, J=10.7 &2.9 Hz); 6.09 (1H, doublet, J=16.1 Hz); 6.18 (1H, doublet of doublets,J=10.7 & 8.7 Hz); 6.84 (1H, singlet); 7.42 (1H, doublet of doublets,J=16.0 & 8.7 Hz); 10.78 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1772, 1730.

EXAMPLE 1214,16-Bis(2,2,2-trichloroethoxycarbonylaminohexanoyl)radicicol

182 mg of radicicol were dissolved in 6 ml of dry tetrahydrofuran, and383 mg of 2,2,2-trichloroethoxycarbonylaminohexanoic acid, 363 mg ofdicyclohexylcarbodiimide and a catalytic amount of dimethylaminopyridinewere added at room temperature to the resulting solution; it was thenstirred at the same temperature for 2 hours. At the end of this time,the dicyclohexylurea which was produced by a side reaction was filteredoff. Water was added to the filtrate and the resulting mixture wasextracted with ethyl acetate. The ethyl acetate solution was washed withan aqueous solution of sodium bicarbonate and then with water, afterwhich it was dried over anhydrous magnesium sulfate. The solvent wasthen removed by distillation under reduced pressure. The resultingresidue was purified by silica gel column chromatography, using a 1:1 byvolume mixture of hexane and ethyl acetate as the eluent. Aftercondensation of the eluate having an Rf value of 0.75 (developingsolvent, ethyl acetate:hexane=2:1 by volume), 191 mg of the titlecompound was obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.15-1.98(13H, multiplet); 1.53 (3H, doublet, J=6.3 Hz); 2.40-2.46 (1H,multiplet); 2.50-2.56 (2H, multiplet); 2.61 (2H, triplet, J=7.3 Hz);3.00-3.04 (1H, multiplet); 3.24 (2H, triplet, J=6.8 Hz); 3.29 (2H,triplet, J=6.9 Hz); 3.52 (1H, multiplet); 3.93, 4.01 (2H, AB-quartet,J=16.1 Hz); 4.72 (4H, singlet); 4.95-5.04 (1H, multiplet); 5.06-5.17(1H, multiplet); 5.40-5.45 (1H, multiplet); 5.80 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,doublet of doublets, J=10.2 & 10.7 Hz); 7.03 (1H, singlet); 7.53 (1H,doublet of doublets, J=10.7 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

EXAMPLE 13 16-(2,2,2-Trichloroethoxycarbonylaminohexanoyl)radicicol

The eluate having an Rf value of 0.51 (developing solvent, ethylacetate:hexane=2:1 by volume) in the silica gel column chromatography ofthe mixture obtained as described in Example 12 was condensed, to give28 mg of the title compound.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.53 (3H,doublet, J=6.3 Hz); 1.42-1.78 (7H, multiplet); 2.35-2.44 (1H,multiplet); 2.50-2.56 (2H, multiplet); 2.98-3.04 (1H, multiplet); 3.25(1H, triplet, J=6.4 Hz); 3.27 (1H, triplet, J=6.3 Hz); 3.56 (1H,multiplet); 4.01, 4.02 (2H, AB-quartet, J=16.1 Hz); 4.72 (2H, singlet);5.08-5.16 (1H, multiplet); 5.38-5.48 (1H, multiplet); 5.79 (1H, doubletof doublets, J=10.8 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.11 (1H,singlet); 6.15 (1H, doublet of doublets, J=10.8 & 10.2 Hz); 6.78 (1H,singlet); 7.58 (1H, doublet of doublets, J=16.0 & 10.2 Hz).

EXAMPLE 14 14,16-Di(methoxyacetyl)radicicol

82 mg of radicicol, 4 ml of dry methylene chloride, 255 μl of pyridine,a catalytic amount of dimethylaminopyridine and 412 mg of methoxyacetylchloride were reacted together, and then the product was treated, ineach case in a similar manner to that described in Example 4, to give amixture. This mixture was purified by silica gel short columnchromatography using a 3:1 by volume mixture of ethyl acetate and hexaneas the eluent, to give 255 mg of the title compound as an oilysubstance.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.54 (3H,doublet, J=6.3 Hz); 1.53-1.68 (1H, multiplet); 2.37-2.43 (1H,multiplet); 2.98-3.05 (1H, multiplet); 3.50 (3H, singlet); 3.52 (1H,multiplet); 3.53 (3H, singlet); 3.95, 4.07 (2H, AB-quartet, J=16.1 Hz);4.23 (2H, singlet); 4.33 (2H, singlet); 5.36-5.46 (1H, multiplet); 5.78(1H, doublet of doublets, J=11.2 & 3.9 Hz); 6.06 (1H, doublet, J=16.1Hz); 6.15 (1H, doublet of doublets, J=11.2 & 10.8 Hz); 7.26 (1H,singlet); 7.49 (1H, doublet of doublets, J=16.0 & 10.8 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1792, 1740.

EXAMPLE 15 14-Methoxyacetylradicicol

1.54 g of 14,16-di(methoxyacetyl)radicicol (prepared as described inExample 14) was dissolved in 20 ml of ethyl acetate, and 15 g of silicagel were added to the resulting solution; the mixture was then stirredfor 23 hours at room temperature. At the end of this time, the silicagel was removed by filtration, and the solution was washed well withethyl acetate. The filtrate and the washings were combined and condensedby evaporation under reduced pressure, and the resulting residue waspurified by silica gel column chromatography using a 2:1 by volumemixture of ethyl acetate and hexane as the eluent. The eluate having anRf value of 0.50 (developing solvent, ethyl acetate:hexane=2:1 byvolume) was collected and condensed, to give 340 mg of the titlecompound as an oily substance.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.53 (3H,doublet, J=6.8 Hz); 1.86-1.97 (1H, multiplet); 2.34-2.42 (1H,multiplet); 2.92-2.97 (1H, multiplet); 3.17 (1H, multiplet); 3.53 (3H,singlet); 3.98, 4.70 (2H, AB-quartet, J=16.6 Hz); 5.51-5.60 (1H,multiplet); 5.84 (1H, doublet of doublets, J=10.7 & 2.9 Hz); 6.10 (1H,doublet, J=16.1 Hz); 6.18 (1H, doublet of doublets, J=10.7 & 9.2 Hz);6.89 (1H, singlet); 7.42 (1H, doublet of doublets, J=17.0 & 9.2 Hz);0.79 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1790, 1725.

EXAMPLE 16 16-Methoxyacetylradicicol

The eluate having an Rf value of 0.42 (developing solvent, ethylacetate:hexane=2:1 by volume) obtained in the course of the silica gelcolumn chromatography described in Example 15 was collected andcondensed, to give 357 mg of the title compound.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.51 (3H,doublet, J=6.9 Hz); 1.58-1.67 (1H, multiplet); 2.34-2.42 (1H,multiplet); 2.98-3.04 (1H, multiplet); 3.51 (3H, singlet); 3.52 (1H,multiplet); 4.00, 4.13 (2H, AB-quartet, J=16.1 Hz); 4.24 (2H, singlet);5.32-5.42 (1H, multiplet); 5.77 (1H, doublet of doublets, J=10.7 & 3.9Hz); 5.99 (1H, singlet); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,doublet of doublets, J=10.7 & 10.2 Hz); 6.82 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.0 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1782, 1730.

EXAMPLE 17 14,16-Di(benzoyl)radicicol

Following a procedure similar to that described in Example 4, 1.459 g ofradicicol, 37 ml of dry methylene chloride, 1.9 ml of pyridine, acatalytic amount of dimethylaminopyridine and 618 mg of benzoyl chloridewere reacted together, and the product was treated, to give 965 mg ofthe title compound as crystals.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.24-1.38(1H, multiplet); 1.39 (3H, doublet, J=6.3 Hz); 2.13-2.20 (1H,multiplet); 2.94-2.99 (1H, multiplet); 3.61 (1H, multiplet); 3.97, 4.23(2H, AB-quartet, J=16.1 Hz); 5.09-5.18 (1H, multiplet); 5.77 (1H,doublet of doublets, J=10.7 & 4.3 Hz); 6.08 (1H, doublet, J=16.1 Hz);6.17 (1H, doublet of doublets, J=10.7 & 7.3 Hz); 7.26 (1H, singlet);7.43-7.71 (6H, multiplet); 8.17 (1H, doublet of doublets, J=17.0 & 7.3Hz); 8.12-8.23 (4H, multiplet).

Infrared Absorption Spectrum (Nujol) ν_(max) cm⁻¹ : 1748, 1728.

Elemental analysis: Calculated for C₃₂ H₂₅ O₈ Cl: C, 67.08%; H, 4.40%;Cl, 6.19%. Found: C, 67.11%; H, 4.58%; Cl, 6.25%.

EXAMPLE 18 14-Benzoylradicicol

After the silica gel column chromatography described in Example 17, 756mg of the title compound having an Rf value of 0.61 (developing solvent,ethyl acetate:hexane=2:1 by volume) was obtained as an oily substance.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.56 (3H,doublet, J=6.8 Hz); 1.88-1.98 (1H, multiplet); 2.34-2.44 (1H,multiplet); 2.93-2.98 (1H, multiplet); 3.20 (1H, multiplet); 4.02, 4.72(2H, AB-quartet, J=16.6 Hz); 5.55-5.65 (1H, multiplet); 6.12 (1H,doublet, J=16.6 Hz); 6.21 (1H, doublet of doublets, J=10.7 & 10.4 Hz);7.03 (1H, singlet); 7.45 (1H, doublet of doublets, J=14.0 & 8.7 Hz);7.41-7.70 (3H, multiplet); 8.18 (2H, multiplet); 10.82 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1750.

EXAMPLE 19 14,16-Di(phenoxyacetyl)radicicol

Following a procedure similar to that described in Example 4, 1.459 g ofradicicol, 37 ml of dry methylene chloride, 1.9 ml of pyridine, acatalytic amount of dimethylaminopyridine and 819 mg of phenoxyacetylchloride were reacted together, and the product was treated, to give 661mg of the title compound as an oily substance.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.33-1.43(1H, multiplet); 1.50 (3H, doublet, J=6.3 Hz); 2.21-2.31 (1H,multiplet); 2.94-2.99 (1H, multiplet); 3.44 (1H, multiplet); 3.95, 4.03(2H, AB-quartet, J=16.6 Hz); 4.82 (2H, singlet); 4.93 (2H, singlet);5.29-5.38 (1H, multiplet); 5.78 (1H, doublet of doublets, J=10.7 & 3.4Hz); 6.05 (1H, doublet, J=16.2 Hz); 6.13 (1H, doublet of doublets,J=10.7 & 10.7 Hz); 6.93-7.17 (6H, multiplet); 7.27 (1H, singlet);7.30-7.38 (4H, multiplet); 7.51 (1H, doublet of doublets, J=16.0 & 10.7Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1796, 1738.

EXAMPLE 20 14,16-Di(phenylacetyl)radicicol

Following a procedure similar to that described in Example 4, butreacting 1.641 g of radicicol, 40 ml of dry methylene chloride, 2.14 mlof pyridine, a catalytic amount of dimethylaminopyridine and 765 mg ofphenylacetyl chloride, 926 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.98-1.08(1H, multiplet); 1.43 (3H, doublet, J=6.4 Hz); 2.07-2.17 (1H,multiplet); 2.85-2.93 (1H, multiplet); 3.36 (1H, multiplet); 3.71-3.98(2H, multiplet); 3.88 (4H, singlet); 4.93-5.05 (1H, multiplet); 5.75(1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.00 (1H, doublet, J=16.1Hz); 6.09 (1H, doublet of doublets, J=10.7 & 10.3 Hz); 6.98 (1H,singlet); 7.30-7.36 (10H, multiplet); 7.45 (1H, doublet of doublets,J=16.0 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1775, 1745.

EXAMPLE 21 14-Phenylacetylradicicol

After the silica gel column chromatography described in Example 20, 403mg of the title compound having an Rf value of 0.43 (developing solvent,ethyl acetate:hexane=1:1 by volume) were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.53 (3H,doublet, J=6.8 Hz); 1.85-1.95 (1H, multiplet); 2.35-2.43 (1H,multiplet); 2.91-2.96 (1H, multiplet); 3.14 (1H, multiplet); 3.90 (2H,singlet); 3.95, 4.67 (2H, AB-quartet, J=16.2 Hz); 5.51-5.58 (1H,multiplet); 5.82 (1H, doublet of doublets, J=10.8 & 2.9 Hz); 6.08 (1H,doublet, J=16.6 Hz); 6.16 (1H, doublet of doublets, J=10.8 & 9.3 Hz);6.82 (1H, singlet); 7.35 (5H, multiplet); 7.40 (1H, doublet of doublets,J=16.0 & 9.3 Hz); 0.76 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1728.

EXAMPLE 22 14,16-Di(chloroacetyl)radicicol

Following a procedure similar to that described in Example 4, but using1.82 g of radicicol, 40 ml of dry methylene chloride, 2.55 ml ofpyridine, a catalytic amount of dimethylaminopyridine and 1.24 ml ofchloroacetyl chloride, 2.6 g of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.55 (3H,doublet, J=6.4 Hz); 1.52-1.66 (1H, multiplet); 2.36-2.46 (1H,multiplet); 2.98-3.05 (1H, multiplet); 3.48 (1H, multiplet); 3.94, 4.06(2H, AB-quartet, J=16.6 Hz); 4.24 (2H, singlet); 4.34 (2H, singlet);5.38-5.48 (1H, multiplet); 5.80 (1H, doublet of doublets, J=11.0 & 3.4Hz); 6.06 (1H, doublet, J=16.2 Hz); 6.15 (1H, doublet of doublets,J=11.0 & 10.3 Hz); 7.25 (1H, singlet); 7.49 (1H, doublet of doublets,J=16.2 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1795, 1765, 1740.

EXAMPLE 23 14,16-Di(2-thenoyl)radicicol

Following a procedure similar to that described in Example 4, but using1.094 g of radicicol, 28 ml of dry methylene chloride, 1.4 ml ofpyridine, a catalytic amount of dimethylaminopyridine and 528 mg of2-thenoyl chloride, 1.39 g of the title compound was obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.43 (3H,doublet, J=6.8 Hz); 1.34-1.45 (1H, multiplet); 2.18-2.26 (1H,multiplet); 2.96-3.03 (1H, multiplet); 3.58 (1H, multiplet); 3.96, 4.23(2H, AB-quartet, J=16.1 Hz); 5.14-5.26 (1H, multiplet); 5.76 (1H,doublet of doublets, J=11.0 & 4.3 Hz); 6.07 (1H, doublet, J=16.1 Hz);6.16 (1H, doublet of doublets, J=11.0 & 10.2 Hz); 7.18-7.21 (2H,multiplet); 7.26 (1H, singlet); 7.45 (1H, doublet of doublets, J=16.6 &10.2 Hz); 7.72 (2H, multiplet); 7.96-8.03 (2H, multiplet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1745, 1725.

Elemental analysis Calculated for C₂₈ H₂₁ O₈ ClS₂ : C, 57.40%; H, 3.62%;Cl, 6.06%. Found: C, 57.61%; H, 3.76%; Cl, 5.93%.

EXAMPLE 24 14-(2-Thenoyl)radicicol

After the silica gel column chromatography described in Example 23, 204mg of the title compound having an Rf value of 0.27 (developing solvent,benzene:ethyl acetate=6:1 by volume) was obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.55 (3H,doublet, J=6.9 Hz); 1.87-1.98 (1H, multiplet); 2.34-2.43 (1H,multiplet); 2.93-2.98 (1H, multiplet); 3.18 (1H, multiplet); 4.05, 4.71(2H, AB-quartet, J=16.0 Hz); 5.53-5.65 (1H, multiplet); 5.85 (1H,doublet of doublets, J=10.7 & 2.4 Hz); 6.12 (1H, doublet, J=10.7 Hz);6.19 (1H, doublet of doublets, J=10.7 & 9.3 Hz); 7.04 (1H, singlet);7.18-7.21 (1H, multiplet); 7.44 (1H, doublet of doublets, J=16.0 & 9.3Hz); 7.70-7.73 (1H, multiplet); 8.00 (1H, multiplet); 10.80 (1H,singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1740, 1720.

EXAMPLE 25 14-Stearoyl-16-palmitoylradicicol

Following a procedure similar to that described in Example 4, but using442 mg of 14-stearoylradicicol (prepared as described in Example 7), 20ml of dry methylene chloride, 186 μl of pyridine, a catalytic amount ofdimethylaminopyridine and 202 mg of palmitoyl chloride, and thenpurifying the reaction mixture by silica gel column chromatography usinga 2:1 by volume mixture of hexane and ethyl acetate, 581 mg of the titlecompound were obtained as crystals. Recrystallization of this productfrom pentane afforded 302 mg of white crystals.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.3 Hz); 1.22-1.42 (52H, multiplet); 1.54 (3H, doublet, J=6.8Hz); 1.48-1.62 (1H, multiplet); 1.64-1.81 (4H, multiplet); 2.35-2.44(1H, multiplet); 2.49 (2H, triplet, J=6.8 Hz); 2.58 (2H, triplet, J=7.3Hz); 2.97-3.04 (1H, multiplet); 3.54 (1H, multiplet); 3.91, 4.03 (2H,AB-quartet, J=16.6 Hz); 5.36-5.45 (1H, multiplet); 5.78 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.2 Hz); 6.14 (1H,doublet of doublets, J=10.7 & 10.3 Hz); 7.01 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

EXAMPLE 26 14,16-Di(10-undecenoyl)radicicol

Following a procedure similar to that described in Example 1, but using1459 mg of radicicol, 973 mg of 10-undecenoyl chloride, 37 ml of drymethylene chloride, 1.9 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 840 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.25-1.80(24H, multiplet); 1.48-1.58 (1H, multiplet); 1.53 (3H, doublet, J=6.3Hz); 1.99-2.10 (4H, multiplet); 2.35-2.47 (1H, multiplet); 2.49 (2H,triplet, J=7.7 Hz); 2.58 (2H, triplet, J=7.3 Hz); 2.93-3.04 (1H,multiplet); 3.51 (1H, multiplet); 3.91 & 4.03 (2H, AB-quartet, J=16.1Hz); 4.90-5.04 (2H×2, multiplet); 5.35-5.46 (1H, multiplet); 5.74-5.90(3H, multiplet); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H, doublet ofdoublets, J=10.7 & 10.2 Hz); 7.01 (1H, singlet); 7.52 (1H, doublet ofdoublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Mass spectrum (m/e): 696 (M⁺)

Elemental analysis: Calculated for C₄₀ H₅₃ O₈ Cl: C, 68.90%; H, 7.66%;Cl, 5.08%. Found: C, 68.02%; H, 7.53%, Cl, 5.41%.

EXAMPLE 27 14-(10-Undecenoyl)radicicol

The reaction mixture obtained in the final product treatment employed inExample 26 was fractionated and purified by chromatography throughsilica gel using a 2:1 by volume mixture of hexane and ethyl acetate asthe eluent, to give 360 mg of the title compound having an Rf value of0.3 (developing solvent, a 2:1 by volume mixture of hexane and ethylacetate).

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.25-1.48(12H, multiplet); 1.55 (3H, doublet, J=6.8 Hz); 1.70-1.82 (2H,multiplet); 1.86-1.98 (1H, multiplet); 2.02-2.10 (2H, multiplet);2.33-2.43 (1H, multiplet); 2.59 (2H, triplet, J=7.3 Hz); 2.93-2.98 (1H,multiplet); 3.17 (1H, multiplet); 3.97 and 4.69 (2H, AB-quartet, J=16.6Hz); 4.92-5.03 (2H, multiplet); 5.51-5.62 (1H, multiplet); 5.73-5.90(2H, multiplet); 6.10 (1H, doublet, J=16.1 Hz); 6.18 (1H, doublet ofdoublets, J=10.2, 9.28 Hz); 6.84 (1H, singlet); 7.43 (1H, doublet ofdoublets, J=16 1, 9.2 Hz); 10.78 (1H, singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1730.

Mass spectrum (m/e): 530 (M⁺), 364.

EXAMPLE 28 14,16-Di(2-thenoyl)radicicol

Following a procedure similar to that described in Example 1, but using1094 mg of radicicol, 528 mg of 2-thenoyl chloride, 28 ml of drymethylene chloride, 1.4 ml of pyridine and a catalytic amount ofdimethylaminopyridine 1.0 g of the title compound was obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.43 (3H,doublet, J=6.8 Hz); 1.34-1.45 (1H, multiplet); 2.18-2.26 (1H,multiplet); 2.96-3.03 (1H, multiplet); 3.58 (1H, multiplet); 3.96 & 4.23(2H, AB-quartet, J=16.1 Hz); 5.14-5.26 (1H, multiplet); 5.76 (1H,doublet of doublets, J=11.0 & 4.3 Hz); 6.07 (1H, doublet, J=16.1 Hz);6.16 (1H, doublet of doublets, J=11.0 & 10.2 Hz); 7.18-7.21 (2H,multiplet); 7.26 (1H, singlet); 7.45 (1H, doublet of doublets, J=16.6 &10.2 Hz); 7.72 (2H, multiplet); 7.96-8.03 (2H, multiplet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1745, 1725.

Mass spectrum (m/e): 584 (M⁺), 473.

Elemental analysis: Calculated for C₂₈ H₂₁ O₈ ClS₂ : C, 57.40%; H,3.62%; Cl, 6.06%. Found: C, 57.61%; H, 3.76%; Cl, 5.93%.

EXAMPLE 29 14-(2-Thenoyl)radicicol

The reaction mixture obtained in the final product treatment employed inExample 28 was fractionated and purified by chromatography throughsilica gel, using a 6:1 by volume mixture of benzene and ethyl acetateas the eluent, to give 204 mg of the title compound having an Rf valueof 0.27 (developing solvent, a 6:1 by volume mixture of benzene andethyl acetate).

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.55 (3H,doublet, J=6.9 Hz); 1.87-1.98 (1H, multiplet); 2.34-2.43 (1H,multiplet); 2.93-2.98 (1H, multiplet); 3.18 (1H, multiplet); 4.05 & 4.71(2H, AB-quartet, J=16.0 Hz); 5.53-5.65 (1H, multiplet); 5.85 (1H,doublet of doublets, J=10.7 & 2.4 Hz); 6.12 (1H, doublet, J=17.0 Hz);6.19 (1H, doublet of doublets, J=10.7 & 9.3 Hz); 7.04 (1H, singlet);7.18-7.21 (1H, multiplet); 7.44 (1H, doublet of doublets, J=16.0 & 9.3Hz); 7.70-7.73 (1H, multiplet); 8.00 (1H, multiplet); 10.21 (1H,singlet).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1740, 1720.

Mass spectrum (m/e): 474 (M⁺), 364.

EXAMPLE 30 14-Elaidoyl-16-palmitoylradicicol

Following a procedure similar to that described in Example 25, but using500 mg of 14-elaidoylradicicol, 303 mg of palmitoyl chloride, 20 ml ofdry methylene chloride, 0.2 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 484 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.87 (6H,triplet, J=6.8 Hz); 1.2-18 (48H, multiplet); 1.53 (3H, doublet, J=6.3Hz); 1.92-2.00 (4H, multiplet); 2.35-2.45 (1H, multiplet); 2.49 (2H,triplet, J=7.8 Hz); 2.58 (2H, triplet, J=7.3 Hz); 2.96-3.05 (1H,multiplet); 3.52 (1H, multiplet); 3.91 & 4.03 (2H, AB-quartet, J=16.6Hz); 5.36-5.47 (3H, multiplet); 5.78 (1H, doublet of doublets, J=10.7 &3.4 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.14 (1H, doublet of doublets,J=18.7 & 10.2 Hz); 7.01 (1H, singlet); 7.51 (1H, doublet of doublets,J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis Calculated for C₅₂ H₇₉ O₈ Cl: C, 71.98%; H, 9.18%;Cl, 4.09%. Found: C, 71.26%; H, 9.45%; Cl, 3.93%.

EXAMPLE 31 14,16-Dimyristoylradicicol

Following a procedure similar to that described in Example 1, but using1.28 g of radicicol, 1.04 g of myristoyl chloride, 35 ml of drymethylene chloride, 1.76 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 0.80 g of the title compound was obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.6 Hz); 1.2-1.5 (40H, multiplet); 1.54 (3H, doublet, J=6.8Hz); 1.45-1.6 (1H, multiplet); 1.6-1.8 (4H, multiplet); 2.35-2.45 (1H,multiplet); 2.50 (2H, triplet, J=6.8 Hz); 2.59 (2H, triplet, J=7.5 Hz);2.98-3.04 (1H, multiplet); 3.50-3.53 (1H, multiplet); 3.92 (1H, doublet,J=16.4 Hz); 4.03 (1H, doublet, J=16.4 Hz); 5.3-5.5 (1H, multiplet); 5.79(1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, 16.1 Hz);6.15 (1H, doublet of doublets, J=10.7 & 10.3 Hz); 7.02 (1H, singlet);7.52 (1H, doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₄₆ H₆₉ O₈ Cl: C, 70.34%; H, 8.85%;Cl, 4.51%. Found: C, 70.43%; H, 8.68%; Cl, 4.46%.

EXAMPLE 32 14-Myristoylradicicol

The reaction mixture obtained in the final product treatment employed inExample 31 was fractionated and purified by chromatography throughsilica gel, using a 2:1 by volume mixture of hexane and ethyl acetate asthe eluent, to give 543 mg of the title compound having an Rf value of0.7 (developing solvent, a 1:1 by volume mixture of hexane and ethylacetate).

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.26 (3H,triplet, J=6.9 Hz); 1.2-1.5 (20H, multiplet); 1.55 (3H, doublet, J=6.8Hz); 1.7-1.8 (2H, multiplet); 1.85-2.0 (1H, multiplet); 2.38 (1H,doublet of triplets, J=15.6 & 3.4 Hz); 2.59 (2H, triplet, J=7.5 Hz);2.95 (1H, doublet of triplets, J=8.8 & 2.4 Hz); 3.16 (1H, multiplet);3.98 (1H, doublet, J=16.6 Hz); 4.69 (1H, doublet, J=16.6 Hz); 5.52-5.59(1H, multiplet); 5.84 (1H, doublet of doublets, J=10.7 & 2.4 Hz); 6.10(1H, doublet, J=16.1 Hz); 6.18 (1H, doublet of doublets, J=10.7 & 10.3Hz); 6.84 (1H, singlet); 7.43 (1H, doublet of doublets, J=16.1 & 10.3Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770.

Elemental analysis: Calculated for C₃₂ H₄₃ O₇ Cl: C, 66.83%; H, 7.54%;Cl, 6.16%. Found: C, 66.83%; H, 7.60%; Cl, 6.01%.

EXAMPLE 33 14-Myristoyl-16-palmitoylradicicol

Following a procedure similar to that described in Example 25, but using539 mg of 14-myristoylradicicol, 509 mg of palmitoyl chloride, 15 ml ofdry methylene chloride, 0.47 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 742 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.6 Hz); 1.2-1.5 (44H, multiplet); 1.54 (3H, doublet, J=6.8Hz); 1.5-1.6 (1H, multiplet); 1.6-1.8 (4H, multiplet); 2.3-2.45 (1H,multiplet); 2.50 (2H, triplet, J=7.3 Hz); 2.59 (2H, triplet, J=7.6 Hz);2.98-3.04 (1H, multiplet); 3.51-3.52 (1H, multiplet); 3.92 (1H, doublet,J=16.1 Hz); 4.03 (1H, doublet, J=16.1 Hz); 5.38-5.43 (1H, multiplet);5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet,J=16.1 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 10.3 Hz); 7.02 (1H,singlet); 7.52 (1H, doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

Elemental analysis: Calculated for C₄₈ H₇₃ O₈ Cl: C, 70.87%; H, 9.04%;Cl, 4.36%. Found: C, 70.21%; H, 9.32%; Cl, 3.95%.

EXAMPLE 34 14,16-Dilinoleoylradicicol

Following a procedure similar to that described in Example 1, but using814 mg of radicicol, 800 mg of linoleoyl chloride, 22 ml of drymethylene chloride, 1.09 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 761 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.89 (6H,triplet, J=6.8 Hz); 1.2-1.4 (28H, multiplet); 1.54 (3H, doublet, J=7.8Hz); 1.49-1.61 (1H, multiplet); 1.63-1.80 (4H, multiplet); 2.0-2.1 (8H,multiplet); 2.36-2.44 (1H, multiplet); 2.50 (2H, triplet, J=7.8 Hz);2.59 (2H, triplet, J=7.6 Hz); 2.78 (4H, doublet of doublets, J=5.9 & 5.4Hz); 2.98-3.03 (1H, multiplet); 3.52 (1H, multiplet); 3.92 (1H, doublet,J=16.3 Hz); 4.03 (1H, doublet, J=16.3 Hz); 5.25-5.45 (9H, multiplet);5.79 (1H, doublet of doublets, J=10.3 & 3.7 Hz); 6.06 (1H, doublet,J=16.1 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 10.3 Hz); 7.02 (1H,singlet); 7.52 (1H, doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

Elemental analysis: Calculated for C₅₄ H₇₆ O₈ Cl: C, 72.99%; H, 8.62%;Cl, 3.99%. Found: C, 72.89%; H, 8.79%; Cl, 3.94%.

EXAMPLE 35 14-Linoleoylradicicol

The reaction mixture obtained in the final product treatment employed inExample 34 was fractionated and purified by chromatography throughsilica gel, using a 2:1 by volume mixture of hexane and ethyl acetate asthe eluent, to give 662 mg of the title compound having an Rf value of0.72 (developing solvent, a 1:1 by volume mixture of hexane and ethylacetate).

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.89 (3H,triplet, J=6.3 Hz); 1.2-1.5 (14H, multiplet); 1.55 (3H, doublet, J=6.8Hz); 1.5-1.8 (3H, multiplet); 1.8-2.3 (4H, multiplet); 2.38 (1H, doubletof triplets, J=15.1 & 3.4 Hz); 2.60 (3H, triplet, J=7.2 Hz); 2.78 (1H,triplet, J=5.9 Hz); 2.9-3.0 (1H, multiplet); 3.17 (1H, broad singlet);3.98 (1H, doublet, J=16.9 Hz); 4.38 (1H, doublet, J=16.9 Hz); 5.25-5.45(2H, multiplet); 5.5-5.7 (3H, multiplet); 5.86 (1H, doublet of doublets,J=10.2 & 5.8 Hz); 6.11 (1H, doublet, J=16.1 Hz); 6.18 (1H, triplet,J=9.3 Hz); 6.84 (1H, singlet); 7.43 (1H, doublet of doublets, J=16.1 &9.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1730.

EXAMPLE 36 14,16-Diretinoylradicicol

Following a procedure similar to that described in Example 12, but using277 mg of radicicol, 665 mg of trans-vitamin A acid (trans-retinoicacid), 10 ml of dry tetrahydrofuran, 470 mg of dicyclohexylcarbodiimideand a catalytic amount of dimethylaminopyridine, 388 mg of the titlecompound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.03 (6H,singlet); 1.04 (6H, singlet); 1.4-1.7 (9H, multiplet); 1.50 (3H,doublet, J=6.8 Hz); 1.72 (6H, singlet); 2.02 (3H, singlet); 2.03 (3H,singlet); 1.95-2.1 (4H, multiplet); 2.25-2.4 (1H, multiplet); 2.38 (3H,singlet); 2.39 (3H, singlet); 2.95-3.0 (1H, multiplet); 3.63 (1H,multiplet); 3.92 (1H, doublet, J=15.6 Hz); 4.15 (1H, doublet, J=15.6Hz); 5.2-5.3 (1H, multiplet); 5.74 (1H, doublet of doublets, J=11.2, 4.9Hz); 5.92 (1H, singlet); 5.99 (1H, singlet); 6.06 (1H, doublet, J=16.1Hz); 6.1-6.25 (3H, multiplet); 6.25-6.4 (4H, multiplet); 7.10 (1H,singlet); 7.05-7.18 (2H, multiplet); 7.46 (1H, doublet of doublets,J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1740.

Elemental analysis: Calculated for C₄₂ H₄₅ O₈ Cl: C, 70.73%; H, 6.36%;Cl, 4.97%. Found: C, 70.38%; H, 6.46%; Cl, 4.66%.

EXAMPLE 37 14-(10-Undecenoyl)-16-palmittoylradicicol

Following a procedure similar to that described in Example 1, but using400 mg of 14-(10-undecenoyl)radicicol (prepared as described in Example27), 329 mg of palmitoyl chloride, 15 ml of dry methylene chloride, 0.19ml of pyridine and a catalytic amount of dimethylaminopyridine, 477 mgof the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (3H,triplet, J=6.8 Hz) 1.2-1.8 (39H, multiplet); 1.53 (3H, doublet, J=6.3Hz); 2.00-2.10 (2H, multiplet); 2.36-2.45 (1H, multiplet); 2.49 (2H,triplet, J=6.3 Hz); 2.58 (2H, triplet, J=7.3 Hz); 2.97-3.05 (1H,multiplet); 3.52 (1H, multiplet); 3.91 & 4.03 (2H, AB-quartet, J=16.1Hz); 4.90-5.03 (2H, multiplet); 5.35-5.47 (1H, multiplet); 5.75-5.90(2H, multiplet); 6.06 (1H, doublet, J=16.6 Hz); 6.14 (1H, doublet ofdoublets, J=11.2 & 10.2 Hz); 7.01 (1H, singlet); 7.52 (1H, doublet ofdoublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1766, 1735.

Mass spectrum (m/e): 768 (M⁺), 602, 364.

EXAMPLE 38 14,16-Bis(3-methylthiopropionyl)radicicol

Following a procedure similar to that described in Example 1, but using1.56 g of radicicol, 0.71 g of 3-methylthiopropionyl chloride, 40 ml ofdry methylene chloride, 2.15 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 447 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.54 (3H,triplet, J=6.4 Hz); 2.16 (3H, singlet); 2.17 (3H, singlet); 2.41 (1H,doublet of triplets, J=14.7 & 3.4 Hz); 2.83 (4H, singlet); 2.83-2.95(4H, multiplet); 3.01 (1H, doublet of triplets, J=11.3 & 2.9 Hz); 3.51(1H, multiplet); 3.93 (1H, doublet, J=16.4 Hz); 4.03 (1H, doublet,J=16.4 Hz); 5.42-5.47 (1H, multiplet); 5.80 (1H, doublet of doublets,J=10.7 & 3.4 Hz); 6.07 (1H, doublet, J=16.1 Hz); 6.15 (1H, doublet ofdoublets, J=10.7 & 10.3 Hz); 7.10 (1H, singlet); 7.52 (1H, doublet ofdoublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1775, 1740.

Elemental analysis: Calculated for C₂₆ H₂₉ O₈ S₂ Cl: C, 54.87%; H, 5.14;Cl, 6.23, S: 11.27%. Found: C, 55.26%; H, 5.37; Cl, 6.14, S: 11.01%.

EXAMPLE 39 14,16-Dipalmitoleoylradicicol

Following a procedure similar to that described in Example 12, but using365 mg of radicicol, 636 mg of palmitoleic acid, 20 ml of dry methylenechloride, 716 mg of dicyclohexylcarbodiimide and a catalytic amount ofdimethylaminopyridine, 654 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.6 Hz); 1.2-1.4 (32H, multiplet); 1.54 (3H, doublet, J=6.8Hz); 1.5-1.6 (1H, multiplet); 1.6-1.8 (4H, multiplet); 1.9-2.1 (8H,multiplet); 2.35-2.45 (1H, multiplet); 2.50 (2H, triplet, J=7.3 Hz);2.59 (2H, triplet, J=7.6 Hz); 2.98-3.04 (1H, multiplet); 3.52 (1H,multiplet); 3.92 (1H, doublet, J=16.4 Hz); 4.03 (1H, doublet, J=16.4Hz); 5.3-5.5 (5H, multiplet); 5.79 (1H, doublet of doublets, J=10.7 &3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets,J=10.7 & 10.3 Hz); 7.02 (1H, singlet); 7.52 (1H, doublet of doublets,J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

Elemental analysis: Calculated for C₅₀ H₇₃ O₈ Cl: C, 71.70%; H, 8.79%;Cl, 4.23%. Found: C, 72.09%; H, 8.89%; Cl, 3.56%.

EXAMPLE 40 14,16-Diisopalmitoylradicicol

Following a procedure similar to that described in Example 12, but using500 mg of radicicol, 878 mg of isopalmitic acid, 20 ml of drytetrahydrofuran, 848 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 1.12 g of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.85-0.9(12H, multiplet); 1.2-1.5 (40H, multiplet); 1.55 (3H, doublet, J=6.4Hz); 1.4-1.9 (9H, multiplet); 2.40 (1H, doublet of doublets, J=14.6 &2.6 Hz); 2.45-2.65 (2H, multiplet); 3.01 (1H, doublet of triplets, J=8.8& 2.6 Hz); 3.53 (1H, multiplet); 3.89 (1H, doublet, J=16.4 Hz); 3.96(1H, doublet, J=16.4 Hz); 5.4-5.5 (1H, multiplet); 5.84 (1H, doublet ofdoublets, J=10.7 & 3.4 Hz); 6.07 (1H, doublet, J=16.1 Hz); 6.15 (1H,triplet, J=10.7 Hz); 6.92 (1H, singlet); 7.62 (1H, doublet of doublets,J=16.1 & 10.7 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

Elemental analysis: Calculated for C₅₀ H₇₇ O₈ Cl: C, 71.36%; H, 9.22%;Cl, 4.21%. Found: C, 71.31%; H, 9.32%; Cl, 3.96%.

EXAMPLE 41 16-Palmitoylradicicol

Following a procedure similar to that described in Example 12, but using364 mg of radicicol, 384 mg of palmitic acid, 15 ml of drytetrahydrofuran, 309 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 62 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (3H,triplet, J=6.3 Hz); 1.51 (3H, doublet, J=6.3 Hz); 1.20-1.76 (27H,multiplet); 2.34-2.43 (1H, multiplet); 2.50 (2H, triplet, J=7.8 Hz);2.96-3.04 (1H, multiplet); 3.56 (1H, multiplet); 3.96 & 4.06 (2H,AB-quartet, J=16.6 Hz); 5.34-5.45 (1H, multiplet); 5.78 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.04 (1H, singlet); 6.06 (1H, doublet,J=16.6 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 10.2 Hz); 6.77 (1H,singlet); 7.56 (1H, doublet of doublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1765, 1730.

Mass spectrum (m/e): 602 (M⁺).

Elemental analysis: Calculated for C₃₄ H₄₇ O₇ Cl: C, 67.70%; H, 7.85%;Cl, 5.88%. Found: C, 67.10%; H, 7.62%; Cl, 5.72%.

EXAMPLE 42 14,16-Di(2-octynoyl)radicicol

Following a procedure similar to that described in Example 12, but using730 mg of radicicol, 701 mg of 2-octynoic acid, 15 ml of drytetrahydrofuran, 1.03 g of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 611 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.91 (3H,triplet, J=6.8 Hz); 0.92 (3H, triplet, J=7.3 Hz); 1.2-1.6 (8H,multiplet); 1.56 (3H, doublet, J=6.8 Hz); 1.5-1.7 (4H, multiplet);1.7-1.8 (1H, multiplet); 2.35-2.47 (5H, multiplet); 3.0-3.1 (1H,multiplet); 3.5-3.55 (1H, multiplet); 3.93 (1H, doublet, J=16.1 Hz);4.26 (1H, doublet, J=16.1 Hz); 5.2-5.35 (1H, multiplet); 5.69 (1H,doublet of doublets, J=10.7 & 5.1 Hz); 6.06 (1H, doublet, J=16.1 Hz);6.15 (1H, doublet of doublets, J=10.7 & 9.8 Hz); 7.11 (1H, singlet);7.34 (1H, doublet of doublets, J=16.1 & 9.8 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 2250, 1745.

Elemental analysis: Calculated for C₃₄ H₃₇ O₈ Cl: C, 67.04%; H, 6.12%%;Cl, 5.82%. Found: C, 66.76%; H, 6.21%%; Cl, 5.76%.

EXAMPLE 43 14,16-Bis(12-allyloxycarbonylaminododecanoyl)radicicol

Following a procedure similar to that described in Example 12, but using547 mg of radicicol, 3.75 g of 12-allyloxycarbonylaminododecanoic acid,15 ml of dry 1-methyl-2-pyrrolidinone, 1.6 g of dicyclohexylcarbodiimideand a catalytic amount of dimethylaminopyridine, 418 mg of the titlecompound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.61(32H, multiplet); 1.54 (3H, doublet, J=6.8 Hz); 1.6-1.8 (4H, multiplet);2.41 (1H, doublet of triplets, J=14.7 & 3.4 Hz); 2.50 (2H, triplet,J=7.3 Hz); 2.58 (2H, triplet, J=7.6 Hz); 3.01 (1H, doublet of triplets,J=8.3 & 4.3 Hz); 3.1-3.2 (4H, multiplet); 3.52 (1H, multiplet); 3.92(1H, doublet, J=16.1 Hz); 4.03 (1H, doublet, J=16.1 Hz); 4.56 (4H,doublet, J=5.4 Hz); 4.72 (2H, broad singlet); 5.20 (2H, doublet ofdoublets, J=10.3 & 1.2 Hz); 5.30 (2H, doublet of doublets, J=17.1 & 1.2Hz); 5.38-5.43 (1H, multiplet); 5.79 (1H, doublet of doublets, J=10.7 &3.9 Hz); 5.85-5.99 (2H, multiplet); 6.06 (1H, doublet, J=16.1 Hz); 6.15(1H, doublet of doublets, J=10.7 & 10.3 Hz); 7.02 (1H, singlet); 7.52(1H, doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1720.

Elemental analysis: Calculated for C₅₀ H₇₁ O₁₂ N₂ Cl: C, 67.74%; H,7.72%; N, 3.02%; Cl, 3.82%. Found: C, 64.75%; H, 7.72%; N, 3.28%; Cl,3.62%.

EXAMPLE 44 14,16-Dipentadecanoylradicicol

Following a procedure similar to that described in Example 12, but using500 mg of radicicol, 830 mg of pentadecanoic acid, 15 ml of drytetrahydrofuran, 707 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 782 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.6 Hz); 1.2-1.5 (44H, multiplet); 1.54 (3H, doublet, J=6.4Hz); 1.5-1.6 (1H, multiplet); 1.6-1.8 (4H, multiplet); 2.40 (1H,triplet, J=13.7 & 3.1 Hz); 2.49 (2H, triplet, J=7.3 Hz); 2.59 (2H,triplet, J=7.6 Hz); 2.99-3.04 (1H, multiplet); 3.52 (1H, multiplet);3.92 (1H, doublet, J=16.1 Hz); 4.03 (1H, doublet, J=16.1 Hz); 5.38-5.43(1H, multiplet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06(1H, doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 10.3Hz); 7.02 (1H, singlet); 7.53 (1H, doublet of doublets, J=16.1 & 10.3Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₄₈ H₇₃ O₈ Cl: C, 70.87%; H, 9.04%;Cl, 4.36%. Found: C, 71.11%; H, 9.16%; Cl, 3.97%.

EXAMPLE 45 14,16-Diheptadecanoylradicicol

Following a procedure similar to that described in Example 1, but using730 mg of radicicol, 693 mg of heptadecanoyl chloride, 25 ml of drymethylene chloride, 1 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 539 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.6 Hz); 1.2-1.5 (52H, multiplet); 1.54 (3H, doublet, J=7.8Hz); 1.5-1.6 (1H, multiplet); 1.6-1.8 (4H, multiplet); 2.40 (1H, doubletof triplets, J=14.7 & 3.4 Hz); 2.49 (2H, triplet, J=7.3 Hz); 2.59 (2H,triplet, J=7.6 Hz); 2.98-3.04 (1H, multiplet); 3.52 (1H, multiplet);3.92 (1H, doublet, J=16.1 Hz); 4.03 (1H, doublet, J=16.1 Hz); 5.38-5.43(1H, multiplet); 5.79 (1H, multiplet); 5.79 (1H, doublet of doublets,J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H, doublet ofdoublets, J=10.7 & 10.3 Hz); 7.02 (1H, singlet); 7.52 (1H, doublet ofdoublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₅₂ H₈₁ O₈ Cl: C, 71.82%; H, 8.39%;Cl, 4.08%. Found: C, 71.98%; H, 9.42%; Cl, 3.93%.

EXAMPLE 46 14-Heptadecanoylradicicol

The reaction mixture obtained in the final product treatment employed inExample 45 was fractionated and purified by chromatography throughsilica gel, using a 3:1 by volume mixture of hexane and ethyl acetate asthe eluent, to give 640 mg of the title compound having an Rf value of0.5 (developing solvent, a 2:1 by volume mixture of hexane and ethylacetate).

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (3H,triplet, J=6.6 Hz); 1.2-1.5 (26H, multiplet); 1.55 (3H, doublet, J=6.8Hz); 1.7-1.85 (2H, multiplet); 1.85-2.0 (1H, multiplet); 2.38 (1H,doublet of triplets, J=16.1 & 2.4 Hz); 2.60 (2H, triplet, J=7.3 Hz);2.92-2.97 (1H, multiplet); 3.17 (1H, multiplet); 3.98 (1H, doublet,J=16.6 Hz); 4.69 (1H, doublet, J=16.6 Hz); 5.52-5.60 (1H, multiplet);5.84 (1H, doublet of doublets, J=10.7 & 2.9 Hz); 6.11 (1H, doublet,J=16.1 Hz); 6.18 (1H, doublet of doublets, J=10.7 & 10.3 Hz); 6.84 (1H,singlet); 7.43 (1H, doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1730.

Elemental analysis: Calculated for C₃₅ H₄₉ O₇ Cl: C, 68.11%; H, 8.00%;Cl, 5.74%. Found: C, 68.55%; H, 8.39%; Cl, 5.27%.

EXAMPLE 4714,16-Bis{16-[(2-trimethylsilylethoxy)methoxy]hexadecanoyl]}radicicol

Following a procedure similar to that described in Example 12, but using121 mg of radicicol, 470 mg of16-[(2-trimethylsilylethoxy)methoxy]hexadecanoic acid, 7 ml of drytetrahydrofuran, 240 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 481 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88-0.95(4H, multiplet); 1.1-2.0 (52H, multiplet); 1.51 (3H, doublet, J=6.8 Hz);2.35-2.60 (5H, multiplet); 3.0 (1H, multiplet); 3.46-3.65 (9H,multiplet); 3.91 (1H, doublet, J=16.1 Hz); 4.00 (1H, doublet, J=16.1Hz); 4.64 (4H, singlet); 5.37 (1H, multiplet); 5.76 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.04 (1H, doublet, J=16.1 Hz); 6.12 (1H,doublet of doublets, J=10.7 & 10.3 Hz); 6.99 (1H, singlet); 7.50 (1H,doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

EXAMPLE 48 14,1,6-Dicinnamoylradicicol

Following a procedure similar to that described in Example 1, but using912 mg of radicicol, 500 mg of cinnamoyl chloride, 30 ml of drymethylene chloride, 1.22 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 442 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.51 (3H,doublet, J=6.4 Hz); 1.5-1.6 (1H, multiplet); 2.33 (1H, doublet oftriplets, J=15.1 & 3.9 Hz); 2.97-3.05 (1H, multiplet); 3.62 (1H,multiplet); 3.96 (1H, doublet, J=16.1 Hz); 4.19 (1H, doublet, J=16.1Hz); 5.25-5.35 (1H, multiplet); 5.77 (1H, doublet of doublets, J=11.2 &4.4 Hz); 6.09 (1H, doublet, J=16.1 Hz); 6.17 (1H, doublet of doublets,J=11.7 & 10.7 Hz); 6.58 (1H, doublet, J=16.1 Hz); 6.62 (1H, doublet,J=16.1 Hz); 7.21 (1H, singlet); 7.4-7.5 (6H, multiplet); 7.49 (1H,doublet of doublets, J=16.1 & 10.3 Hz); 7.55-7.65 (4H, multiplet); 7.87(1H, doublet, J=16.1 Hz); 7.92 (1H, doublet, J=16.1 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1740.

EXAMPLE 49 14-Cinnamoylradicicol

The reaction mixture obtained in the final product treatment employed inExample 48 was fractionated and then purified by chromatography throughsilica gel, using a 2:1 by volume mixture of hexane and ethyl acetate asthe eluent, to give 527 mg of the title compound having an Rf value of0.6 (developing solvent, a 1:1 by volume mixture of hexane and ethylacetate).

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.56 (3H,doublet, J=6.8 Hz); 1.93 (1H, multiplet); 2.39 (1H, doubled doublet ofdoublets, J=15.1 Hz); 2.96 (1H, doubled doublet of doublets, J=8.8 Hz);3.20 (1H, multiplet); 4.01 & 4.70 (2H, AB-quartet, J=16.8 Hz); 5.57 (1H,multiplet); 5.85 (1H, doublet of doublets, J=10.7 & 2.9 Hz); 6.13 (1H,doublet, J=16.1 Hz); 6.20 (1H, doublet of doublets, J=10.7 & 9.3 Hz);6.62 (1H, doublet, J=16.1 Hz); 6.97 (1H, singlet); 7.35-7.5 (4H,multiplet); 7.5-7.65 (2H, multiplet); 7.91 (1H, doublet, J=16.1 Hz).

EXAMPLE 50 14,16-Bis(6-phenylhexanoyl)radicicol

Following a procedure similar to that described in Example 12, but using500 mg of radicicol, 659 mg of 6-phenylhexanoic acid, 15 ml of drytetrahydrofuran, 707 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 704 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.52 (3H,doublet, J=16.4 Hz); 1.3-1.9 (13H, multiplet); 2.37 (1H, doubled doubletof doublets, J=14.6 Hz); 2.45-2.7 (8H, multiplet); 3.00 (1H, doubleddoublet of doublets, J=7.8 Hz); 3.51 (1H, multiplet); 3.91 & 4.02 (2H,AB-quartet, J=16.1 Hz); 5.38 (1H, multiplet); 5.79 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,doublet of doublets, J=11.2 & 10.2 Hz); 6.98 (1H, singlet); 7.1-7.35(10H, multiplet); 7.52 (1H, doublet of doublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1730.

Elemental analysis: Calculated for C₄₂ H₄₅ O₈ Cl: C, 70.73%; H, 6.36%;Cl, 4.97%. Found: C, 70.38%; H, 6.46%; Cl, 4.66%.

EXAMPLE 51 14,16-Di(2-furanacryloyl)radicicol

Following a procedure similar to that described in Example 12, but using500 mg of radicicol, 568 mg of 2-furanacrylic acid, 15 ml of drytetrahydrofuran, 707 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 746 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.51 (3H,doublet, J=6.3 Hz); 1.45-1.6 (1H, multiplet); 2.34 (1H, doubled doubletof doublets, J=14.6 Hz); 2.99 (1H, multiplet); 3.61 (1H, multiplet);3.94 & 4.16 (2H, AB-quartet, J=16.1 Hz); 5.30 (1H, multiplet); 5.76 (1H,doublet of doublets, J=11.2 & 4.4 Hz); 6.08 (1H, doublet, J=16.1 Hz);6.14 (1H, doublet of doublets, J=11.7 & 3.4 Hz); 6.43 (1H, doublet,J=15.6 Hz); 6.48 (1H, doublet, J=15.6 Hz); 6.53 (2H, multiplet); 6.74(2H, multiplet); 7.18 (1H, singlet); 7.47 (1H, doublet of doublets,J=16.1 & 10.3 Hz); 7.59 (1H, doublet, J=15.6 Hz); 7.64 (1H, doublet,J=15.6 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1740.

Elemental analysis: Calculated for C₃₂ H₂₅ O₁₀ Cl: C, 63.53%; H, 4.17%;Cl, 5.86%. Found: C, 63.31%; H, 4.37%; Cl, 5.49%.

EXAMPLE 52 14,16-Di[3-(2-thienyl)acryloyl]radicicol

Following a procedure similar to that described in Example 12, but using365 mg of radicicol, 462 mg of 3-(2-thienyl)acrylic acid, 10 ml of drytetrahydrofuran, 619 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 526 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.51 (3H,doublet, J=6.4 Hz); 1.55 (1H, multiplet); 2.34 (1H, doubled doublet ofdoublets, J=14.6 Hz); 3.01 (1H, doubled doublet of doublets, J=7.2 Hz);3.62 (1H, multiplet); 3.96 & 4.17 (2H, AB-quartet, J=16.1 Hz); 5.30 (1H,multiplet); 5.77 (1H, doublet of doublets, J=10.8 & 4.4 Hz); 6.08 (1H,doublet, J=16.1 Hz); 6.29 (1H, doublet of doublets, J=11.7 & 10.8 Hz);6.35 (1H, doublet, J=15.6 Hz); 6.40 (1H, doublet, J=15.6 Hz); 7.1 (2H,multiplet); 7.18 (1H, singlet); 7.36 (2H, triplet, J=3.4 Hz); 7.48 (3H,multiplet); 7.96 (1H, doublet, J=15.6 Hz); 8.01 (1H, doublet, J=15.6Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1740.

Elemental analysis: Calculated for C₃₂ H₂₅ O₈ S₂ Cl: C, 60.33%; H,3.96%; Cl, 5.56%; S, 10.87%. Found: C, 60.32%; H, 4.26%; Cl, 5.17%; S,9.74%.

EXAMPLE 53 14,16-Bis(12-tritylthioaminododecanoyl)radicicol

Following a procedure similar to that described in Example 12, but using500 mg of radicicol, 2.013 g of 12-tritylthioaminododecanoic acid, 60 mlof dry tetrahydrofuran, 848 mg of dicyclohexylcarbodiimide and acatalytic amount of dimethylaminopyridine, 965 mg of the title compoundwere obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.0-1.8(37H, multiplet); 1.53 (3H, doublet, J=16.3 Hz); 2.40 (1H, doubleddoublet of doublets, J=14.7 Hz); 2.45-2.62 (8H, multiplet); 3.00 (1H,doubled doublet of doublets, J=7.8 Hz); 3.51 (1H, multiplet); 3.91 &4.03 (2H, AB-quartet, J=16.4 Hz); 5.40 (1H, multiplet); 5.78 (1H,doublet of doublets, J=10.7 & 3.4 Hz); 6.06 (1H, doublet, J=16.1 Hz);6.14 (1H, doublet of doublets, J=11.2 & 10.2 Hz); 7.01 (1H, singlet);7.2-7.4 (30H, multiplet); 7.52 (1H, doublet of doublets, J=16.1 & 10.8Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₈₀ H₉₁ O₈ N₂ S₂ Cl: C, 73.45%; H,7.01%; N, 2.14%; Cl, 2.71; S, 4.90%. Found: C, 73.40%; H, 7.17%; N,2.12%; Cl, 3.06; S, 5.01%.

EXAMPLE 54 14,16-Dilinolenoylradicicol

Following a procedure similar to that described in Example 1, but using280 mg of radicicol, 600 mg of linolenoyl chloride, 11 ml of drymethylene chloride, 0.37 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 552 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (hexadeuterated dimethyl sulfoxide,270 MHz) δ ppm: 0.84 (3H, triplet, J=5.4 Hz); 0.85 (3H, triplet, J=6.4Hz); 1.1-1.8 (24H, multiplet); 1.47 (3H, doublet, J=6.3 Hz); 1.5-1.8(1H, multiplet); 1.9-2.2 (8H, multiplet); 2.4-2.5 (1H, multiplet);2.5-2.7 (5H, multiplet); 2.7-2.8 (6H, multiplet); 3.05-3.15 (1H,multiplet); 3.40 (1H, multiplet); 3.84 (1H, doublet, J=16.1 Hz); 4.00(1H, doublet, J=16.1 Hz); 5.2-5.5 (13H, multiplet); 5.78 (1H, doublet ofdoublets, J=10.8 & 3.9 Hz); 6.08 (1H, doublet, J=16.1 Hz); 6.25 (1H,doublet of doublets, J=10.8 & 10.2 Hz); 7.38 (1H, singlet); 7.38 (1H,doublet of doublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₅₄ H₇₃ O₈ Cl: C, 73.24%; H, 8.31%;Cl, 4.00%. Found: C, 73.35%; H, 8.60%; Cl, 3.91%.

EXAMPLE 55 14,16-Bistridecanoylradicicol

Following a procedure similar to that described in Example 12, but using400 mg of radicicol, 588 mg of tridecanoic acid, 6 ml of drytetrahydrofuran, 566 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 688 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.5 Hz); 1.1-1.5 (36H, multiplet); 1.54 (3H, doublet, J=6.3Hz); 1.6-1.8 (5H, multiplet); 2.35-2.45 (1H, multiplet); 2.50 (2H,triplet, J=7.5 Hz); 2.59 (2H, triplet, J=7.5 Hz); 3.02 (1H, multiplet);3.51 (1H, multiplet); 3.86 & 3.97 (2H, AB-quartet, J=13.6 Hz); 5.40 (1H,multiplet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06 (1H,doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets, J=11.3 & 10.3 Hz);7.01 (1H, singlet); 7.52 (1H, doublet of doublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₄₄ H₆₅ O₈ Cl: C, 69.77%; H, 8.65%;Cl, 4.68%. Found: C, 69.54%; H, 8.69%; Cl, 4.66%.

EXAMPLE 56 14,16-Dilauroylradicicol

Following a procedure similar to that described in Example 1, but using730 mg of radicicol, 656 mg of lauroyl chloride, 14 ml of dry methylenechloride, 0.97 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 644 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.6 Hz); 1.2-1.5 (32H, multiplet); 1.54 (3H, doublet, J=6.3Hz); 1.48-1.5 (1H, multiplet); 1.5-1.8 (4H, multiplet); 2.40 (1H,doubled doublet of doublets, J=4.9 Hz); 2.49 (2H, triplet, J=6.6 Hz);2.59 (2H, triplet, J=7.6 Hz); 3.01 (1H, multiplet); 3.51 (1H,multiplet); 3.92 & 4.03 (2H, AB-quartet, J=16.6 Hz); 5.40 (1H,multiplet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06 (1H,doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 9.7 Hz);7.02 (1H, singlet); 7.52 (1H, doublet of doublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₄₂ H₆₁ O₈ Cl: C, 69.16%; H, 8.43%;Cl, 4.86%. Found: C, 69.11%; H, 8.65%; Cl, 4.89%.

EXAMPLE 57 14,16-Bis(16-acetylthiohexadecanoyl)radicicol

Following a procedure similar to that described in Example 12, but using120 mg of radicicol, 206 mg of 16-acetylthiohexadecanoic acid, 5 ml ofdry tetrahydrofuran, 330 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 235 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.8(52H, multiplet); 1.53 (3H, doublet, J=6.3 Hz); 2.31 (6H, singlet);2.34-2.45 (1H, multiplet); 2.50 (2H, triplet, J=7.3 Hz); 2.58 (2H,triplet, J=7.3 Hz); 2.86 (2H×2, triplet, J=7.31 Hz); 2.97-3.05 (1H,multiplet); 3.53 (1H, multiplet); 3.91 & 4.03 (2H, AB-quartet, J=16.1Hz); 5.37-5.45 (1H, multiplet); 5.78 (1H, doublet of doublets, J=10.7 &3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets,J=10.7 & 10.7 Hz); 7.01 ,(1H, singlet); 7.52 (1H, doublet of doublets,J=16.1 & 10.7 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770.

EXAMPLE 58 14,16-Di(11-cyanoundecanoyl)radicicol

Following a procedure similar to that described in Example 1, but using365 mg of radicicol, 11-cyanoundecanoyl chloride (prepared from 1.055 gof 11-cyanoundecanoic acid), 7 ml of dry methylene chloride, 1.21 ml ofpyridine and a catalytic amount of dimethylaminopyridine, 707 mg of thetitle compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.25-1.5(24H, multiplet); 1.54 (3H, doublet, J=6.3 Hz); 1.55-1.85 (9H,multiplet); 2.34 (4H, triplet, J=7.0 Hz); 2.41 (1H, doubled doublet ofdoublets, J=14.7 Hz); 2.50 (2H, doublet of doublets, J=8.3 & 7.3 Hz);2.59 (2H, triplet, J=7.8 Hz); 3.01 (1H, multiplet); 3.51 (1H,multiplet); 3.92 & 4.03 (2H, AB-quartet, J=16.1 Hz); 5.40 (1H,multiplet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06 (1H,doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets, J=11.2 & 10.2 Hz);7.02 (1H, singlet); 7.53 (1H, doublet of doublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 2250, 1770, 1735.

Elemental analysis: Calculated for C₄₂ H₅₅ O₈ N₂ Cl: C, 67.14%; H,7.38%; N, 3.73%; Cl, 4.72%. Found: C, 67.13%; H, 7.53%; N, 3.84%; Cl,4.37%.

EXAMPLE 5914,16-Di[11-(9-fluorenyl)methoxycarbonylaminododecanoyl]radicicol

Following a procedure similar to that described in Example 12, but using67 mg of radicicol, 280 mg of11-(9-fluorenyl)methoxycarbonylaminododecanoic acid, 10 ml of drytetrahydrofuran, 132 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 194 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.45(28H, multiplet); 1.53 (3H, doublet, J=6.3 Hz); 1.45-1.8 (9H,multiplet); 2.40 (1H, doubled doublet of doublets, J=14.6 Hz); 2.49 (2H,doublet of doublets, J=8.3 & 7.3 Hz); 2.58 (1H, triplet, J=7.5 Hz); 3.00(1H, multiplet); 3.19 (4H, multiplet); 3.52 (1H, multiplet); 3.92 & 4.03(2H, AB-quartet, J=16.6 Hz); 4.22 (2H, triplet, J=6.8 Hz); 4.40 (4H,doublet, J=6.8 Hz); 4.76 (2H, broad singlet); 5.40 (1H, multiplet); 5.78(1H, doublet of doublets, J=10.7 & 3.4 Hz); 6.06 (1H, doublet, J=16.1Hz); 6.14 (1H, triplet, J=10.7 Hz); 7.02 (1H, singlet); 7.25-7.45 (8H,multiplet); 7.52 (1H, doublet of doublets, J=16.1 & 10.2 Hz); 7.59 (4H,doublet, J=7.3 Hz); 7.76 (4H, doublet, J=7.3 Hz).

Elemental analysis: Calculated for C₇₂ H₈₃ O₁₂ N₂ Cl: C, 71.83%; H,6.95%; N, 2.33%; Cl, 2.94%. Found: C, 71.72%; H, 7.10%; N, 2.51%; Cl,2.79%.

EXAMPLE 60 14,16-Di(11-methoxycarbonylundecanoyl)radicicol

Following a procedure similar to that described in Example 1, but using300 mg of radicicol, 11-methoxycarbonylundecanoyl chloride (preparedfrom 1 g of 11-methoxycarbonylundecanoic acid), 6 ml of dry methylenechloride, 0.4 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 570 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.45(24H, multiplet); 1.54 (3H, doublet, J=6.8 Hz); 1.5-1.8 (9H, multiplet);2.31 (4H, triplet, J=7.5 Hz); 2.40 (1H, doubled doublet of doublets,J=15.1 Hz); 2.50 (2H, triplet, J=7.0 Hz); 3.0 (1H, multiplet); 3.52 (1H,multiplet); 3.67 (6H, singlet); 3.92 & 4.03 (2H, AB-quartet, J=16.1 Hz);5.4 (1H, multiplet); 5.79 (1H, doublet of doublets, J=11.2 & 3.9 Hz);6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H, triplet, J=10.3 Hz); 7.02 (1H,singlet); 7.52 (1H, doublet of doublets, J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1772, 1740, 1735.

Elemental analysis: Calculated for C₄₄ H₆₁ O₁₂ Cl: C, 64.65%; H, 7.52%;Cl, 4.34%. Found: C, 64.60%; H, 7.49%; Cl, 4.25%.

EXAMPLE 61 14,16-Dicaproylradicicol

Following a procedure similar to that described in Example 1, but using365 mg of radicicol, 460 mg of caproyl chloride, 7 ml of dry methylenechloride, 0.49 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 575 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.89 (6H,triplet, J=6.3 Hz); 1.2-1.5 (24H, multiplet); 1.45-1.6 (1H, multiplet);1.54 (3H, doublet, J=6.6 Hz); 1.6-1.8 (4H, multiplet); 2.41 (1H, dm,J=14.5 Hz); 2.50 (2H, triplet, J=7.3 Hz); 2.59 (2H, triplet, J=7.3 Hz);3.01 (1H, multiplet); 3.52 (1H, multiplet); 3.92 (1H, doublet, J=16.5Hz); 4.03 (1H, doublet, J=16.5 Hz); 5.42 (1H, multiplet); 5.79 (1H,doublet of doublets, J=10.6 & 3.9 Hz); 6.11 (1H, doublet, J=15.9 Hz);6.17 (1H, triplet, J=5.9 Hz); 7.02 (1H, singlet); 7.53 (1H, doublet ofdoublets, J=16.5 & 10.6 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1730.

Elemental analysis: Calculated for C₃₈ H₅₃ O₈ Cl: C, 67.79%; H, 7.93%;Cl, 5.27%. Found: C, 67.76%; H, 7.80%; Cl, 5.02%.

EXAMPLE 62 14,16-Diundecanoylradicicol

Following a procedure similar to that described in Example 1, but using365 mg of radicicol, 450 mg of undecanoyl chloride, 7 ml of drymethylene chloride, 0.49 ml of pyridine and a catalytic amount ofdimethylaminopyridine, 586 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.89 (6H,triplet, J=6.4 Hz); 1.2-1.5 (28H, multiplet); 1.45-1.6 (1H, multiplet);1.54 (3H, doublet, J=6.6 Hz); 1.6-1.8 (4H, multiplet); 2.40 (1H, dm,J=15.2 Hz); 2.50 (2H, triplet, J=7.9 Hz); 2.59 (2H, triplet, J=7.3 Hz);3.0 (1H, multiplet); 3.5 (1H, multiplet); 3.92 (1H, doublet, J=16.2 Hz);4.03 (1H, doublet, J=16.2 Hz); 5.42 (1H, multiplet); 5.79 (1H, doubletof doublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.5 Hz); 6.15 (1H,triplet, J=10.7 Hz); 7.02 (1H, singlet); 7.53 (1H, doublet of doublets,J=16.5 & 10.5 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1730.

Elemental analysis: Calculated for C₄₀ H₅₇ O₈ Cl: C, 68.50%; H, 8.19%;Cl, 5.06%. Found: C, 68.56%; H, 8.04%; Cl, 4.86%.

EXAMPLE 63 14,16-Dieicosanoylradicicol

Following a procedure similar to that described in Example 1, but using300 mg of radicicol, eicosanoyl chloride (prepared from 1.2 g ofeicosanoic acid), 5 ml of dry methylene chloride, 0.4 ml of pyridine anda catalytic amount of dimethylaminopyridine, 646 mg of the titlecompound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.88 (6H,triplet, J=6.3 Hz); 1.2-1.5 (44H, multiplet); 1.45-1.6 (1H, multiplet);1.54 (3H, doublet, J=7.3 Hz); 1.6-1.8 (4H, multiplet); 2.40 (1H, dm,J=14.5 Hz); 2.50 (2H, triplet, J=7.3 Hz); 2.59 (2H, triplet, J=7.3 Hz);3.02 (1H, multiplet); 3.52 (1H, multiplet); 3.92 (1H, doublet, J=16.1Hz); 4.03 (1H, doublet, J=16.1 Hz); 5.40 (1H, multiplet); 5.79 (1H,doublet of doublets, J=10.5 & 3.3 Hz); 6.07 (1H, doublet, J=16.5 Hz);6.15 (1H, triplet, J=10.5 Hz); 7.02 (1H, singlet); 7.53 (1H, doublet ofdoublets, J=16.5 & 10.5 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

Elemental analysis: Calculated for C₅₈ H₉₃ O₈ Cl: C, 73.04%; H, 9.83%;Cl, 3.72%. Found: C, 72.99%; H, 9.93%; Cl, 3.77%.

EXAMPLE 64 14,16-Di(16-hydroxyhexadecanoyl)radicicol

Following a procedure similar to that described in Example 12, but using365 mg of radicicol, 681 mg of 16-hydroxyhexadecanoic acid, 20 ml of drytetrahydrofuran, 516 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 661 mg of the title compound wereobtained as crystals melting at 85°-86° C.

Nuclear Magnetic Resonance Spectrum (CDCl₃ +D₂ O, 270 MHz) δ ppm:1.2-1.5 (48H, multiplet); 1.54 (3H, doublet, J=6.3 Hz); 1.5-1.65 (1H,multiplet); 1.65-1.8 (4H, multiplet); 2.41 (1H, doubled doublet ofdoublets, J=14.7 Hz); 2.50 (2H, doublet of doublets, J=7.8 & 6.8 Hz);2.59 (2H, triplet, J=6.8 Hz); 3.02 (1H, multiplet); 3.51 (1H,multiplet); 3.63 (4H, triplet, J=6.3 Hz); 3.92 (1H, doublet, J=16.1 Hz);4.03 (1H, doublet, J=16.1 Hz); 5.40 (1H, multiplet); 5.79 (1H, doubletof doublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,triplet, J=10.3 Hz); 7.02 (1H, singlet); 7.52 (1H, doublet of doublets,J=16.1 & 10.3 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1738.

Elemental analysis: Calculated for C₅₀ H₇₇ O₁₀ Cl: C, 68.74%; H, 8.88%;Cl, 4.06%. Found: C, 68.62%; H, 8.92%; Cl, 4.32%.

EXAMPLE 65 14,16-Di(12-hydroxydodecanoyl)radicicol

Following a procedure similar to that described in Example 12, but using365 mg of radicicol, 1.8 g of 12-hydroxydodecanoic acid, 20 ml of drytetrahydrofuran, 1 g of dicyclohexylcarbodiimide and a catalytic amountof dimethylaminopyridine, 485 mg of the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.5(32H, multiplet); 1.54 (3H, doublet, J=6.3 Hz); 1.5-1.65 (1H,multiplet); 1.65-1.8 (4H, multiplet); 2.41 (1H, doubled doublet ofdoublets, J=14.7 Hz); 3.02 (1H, multiplet); 2.50 (2H, doublet ofdoublets, J=7.7 & 6.4 Hz); 2.59 (2H, doublet, J=7.3 Hz); 3.52 (1H,multiplet); 3.64 (6H, triplet, J=6.6 Hz); 3.91 (1H, doublet, J=16.1 Hz);4.03 (1H, doublet, J=16.1 Hz) 5.41 (1H, multiplet); 5.79 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,triplet, J=10.2 Hz); 7.02 (1H, singlet); 7.52 (1H, doublet of doublets,J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1735.

Elemental analysis: Calculated for C₄₂ H₆₁ O₁₀ Cl: C, 66.26%; H, 8.08%;Cl, 4.66%. Found: C, 66.22%; H, 7.99%; Cl, 4.38%.

EXAMPLE 66 14,16-Di(10-hydroxydecanoyl)radicicol

Following a procedure similar to that described in Example 12, but using365 mg of radicicol, 471 mg of 10-hydroxydecanoic acid, 25 ml of drytetrahydrofuran, 516 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 332 mg of the title compound wereobtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃ +D₂ O, 270 MHz) δ ppm:1.2-1.5 (24H, multiplet); 1.54 (3H, doublet, J=6.3 Hz); 1.5-1.8 (5H,multiplet); 2.41 (1H, dm, J=14.7 Hz); 2.50 (2H, doublet of doublets,J=8.3 & 6.8 Hz); 2.59 (2H, doublet, J=7.3 Hz); 3.01 (1H, multiplet);3.52 (1H, multiplet); 3.63 (6H, triplet, J=6.8 Hz); 3.92 (1H, doublet,J=16.1 Hz); 4.03 (1H, doublet, J=16.1 Hz); 5.40 (1H, multiplet); 5.79(1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.07 (1H, doublet, J=16.1Hz); 6.15 (1H, doublet of doublets, J=11.2 & 10.3 Hz); 7.02 (1H,singlet); 7.53 (1H, doublet of doublets, J=16.1 & 10.2 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1738.

Elemental analysis: Calculated for C₃₈ H₅₃ O₁₀ Cl: C, 64.71%; H, 7.57%;Cl, 5.03%. Found: C, 64.31%; H, 7.21%; Cl, 5.40%.

EXAMPLE 67 14,16-Dimyristoleoylradicicol

Following a procedure similar to that described in Example 1, but using365 mg of radicicol, myristoleoyl chloride prepared from 900 mg ofmyristoleic acid, 7 ml of dry methylene chloride, 0.97 ml of pyridineand a catalytic amount of dimethylaminopyridine, 510 mg of the titlecompound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 0.89 (6H,triplet, J=6.2 Hz); 1.2-1.5 (24H, multiplet); 1.53 (3H, doublet, J=6.3Hz); 1.45-1.6 (1H, multiplet); 1.6-1.8 (4H, multiplet); 2.02 (8H,doublet, J=5.9 Hz); 2.40 (1H, doubled doublet of doublets, J=14.7 Hz);2.49 (2H, doublet of doublets, J=7.8 & 6.8 Hz); 2.59 (2H, triplet, J=7.3Hz); 3.01 (1H, multiplet); 3.51 (1H, multiplet); 3.92 (1H, doublet,J=16.6 Hz); 4.03 (1H, doublet, J=16.6 Hz); 5.27-5.45 (5H, multiplet);5.79 (1H, doublet of doublets, J=10.7 & 3.4 Hz); 6.06 (1H, doublet,J=16.1 Hz); 6.15 (1H, doublet of doublets, J=11.7 & 10.7 Hz); 7.02 (1H,singlet); 7.51 (1H, doublet of doublets, J=16.6 & 10.7 Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1740.

EXAMPLE 68 14,16-Di(11-carbamoylundecanoyl)radicicol

Following a procedure similar to that described in Example 1, but using365 mg of radicicol, 11-carbamoylundecanoyl chloride prepared from 900mg of 11-carbamoylundecanoic acid, 8 ml of dry methylene chloride, 0.97ml of pyridine and a catalytic amount of dimethylaminopyridine, 273 mgof the title compound were obtained.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.25-1.5(24H, multiplet); 1.54 (3H, doublet, J=6.8 Hz); 1.5-1.8 (9H, multiplet);2.22 (4H, triplet, J=7.6 Hz); 2.41 (1H, doubled doublet of doublets,J=15.1 Hz); 2.50 (2H, triplet, J=7.8 Hz); 2.59 (2H, triplet, J=7.3 Hz);3.00 (1H, multiplet); 3.52 (1H, multiplet); 3.92 (1H, doublet, J=16.1Hz); 4.02 (1H, doublet, J=16.1 Hz); 5.40 (1H, multiplet); 5.45 (4H,broad singlet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06(1H, doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 10.3Hz); 7.02 (1H, singlet); 7.52 (1H, doublet of doublets, J=16.1 & 10.3Hz).

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1730.

Elemental analysis: Calculated for C₄₂ H₅₉ O₁₀ N₂ Cl.1/3CHCl₃ : C,61.47%; H, 7.23%; N, 3.39%; Cl, 8.57%. Found: C, 61.69%; H, 7.31%; N,3.61%; Cl, 8.72%.

EXAMPLE 69 14,16-Di[10-(methoxyethoxymethoxy)decanoyl]radicicol

Following a procedure similar to that described in Example 12, but using400 mg of radicicol, 758 mg of 10-(methoxyethoxymethoxy)decanoic acid, 6ml of dry tetrahydrofuran, 567 mg of dicyclohexylcarbodiimide and acatalytic amount of dimethylaminopyridine, 829 mg of the title compoundwere obtained.

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1775, 1735.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.5(24H, multiplet); 1.54 (3H, doublet, J=6.4 Hz); 1.5-1.8 (5H, multiplet);2.40 (1H, doubled doublet of doublets, J=15.1 Hz); 2.50 (2H, doublet ofdoublets, J=6.6 & 8.0 Hz); 2.59 (2H, triplet, J=7.6 Hz); 3.01 (1H,multiplet); 3.40 (6H, singlet); 3.47-3.52 (9H, multiplet); 3.55-3.65(4H, multiplet); 3.92 (1H, doublet, J=16.1 Hz); 4.03 (1H, doublet,J=16.1 Hz); 4.72 (4H, singlet); 5.41 (1H, multiplet); 5.79 (1H, doubletof doublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,triplet, J=10.3 Hz); 7.02 (1H, singlet); 7.52 (1H, doublet of doublets,J=16.1 & 10.7 Hz).

EXAMPLE 70 14,16-Di[10-(methoxymethoxy)decanoyl]radicicol

Following a procedure similar to that described in Example 12, but using400 mg of radicicol, 595 mg of 10-(methoxymethoxy)decanoic acid, 6 ml ofdry tetrahydrofuran, 567 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 739 mg of the title compound wereobtained.

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1775, 1735.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.25-1.5(24H, multiplet); 1.54 (3H, doublet, J=6.4 Hz); 1.5-1.8 (5H, multiplet);2.40 (1H, doubled doublet of doublets, J=14.7 Hz); 2.50 (2H, doublet ofdoublets, J=7.8 & 6.8 Hz); 2.57 (2H, triplet, J=7.5 Hz); 3.00 (1H,multiplet); 3.36 (6H, singlet); 3.51 (4H, triplet, J=6.1 Hz); 3.5 (1H,multiplet); 3.92 (1H, doublet, J=16.6 Hz); 4.03 (1H, doublet, J=16.6Hz); 4.62 (4H, singlet); 5.41 (1H, multiplet); 5.79 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=6.1 Hz); 6.15 (1H,doublet of doublets, J=10.7 & 9.7 Hz); 7.02 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.6 & 10.3 Hz).

EXAMPLE 71 14,16-Di[12-(methoxyethoxymethoxy)dodecanoyl]radicicol

Following a procedure similar to that described in Example 12, but using400 mg of radicicol, 856 mg of 12-(methoxyethoxymethoxy)dodecanoic acid,6 ml of dry tetrahydrofuran, 567 mg of dicyclohexylcarbodiimide and acatalytic amount of dimethylaminopyridine, 893 mg of the title compoundwere obtained.

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1770, 1738.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.24-1.45(32H, multiplet); 1.54 (3H, doublet, J=6.8 Hz); 1.45-1.6 (1H,multiplet); 1.65-1.77 (4H, multiplet); 2.36-2.44 (1H, multiplet); 2.50(2H, doublet of doublets, J=7.8 & 6.8 Hz); 2.59 (2H, triplet, J=7.3 Hz);2.98-3.04 (1H, multiplet); 3.40 (6H, singlet); 3.51-3.58 (9H,multiplet); 3.68-3.71 (4H, multiplet); 3.97 (2H, AB-quartet, J=16.1 Hz);4.72 (4H, singlet); 5.38-5.43 (1H, multiplet); 5.79 (1H, doublet ofdoublets, J=10.7 & 3.9 Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H,doublet of doublets, J=10.7 & 10.3 Hz); 7.02 (1H, singlet); 7.52 (1H,doublet of doublets, J=16.1 & 10.3 Hz)

EXAMPLE 72 14,16-Di[12-(methoxymethoxy)dodecanoyl]radicicol

Following a procedure similar to that described in Example 12, but using400 mg of radicicol, 716 mg of 12-(methoxymethoxy)dodecanoic acid, 7 mlof dry tetrahydrofuran, 567 mg of dicyclohexylcarbodiimide and acatalytic amount of dimethylaminopyridine, 756 mg of the title compoundwere obtained.

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1767, 1730.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.23-1.47(32H, multiplet); 1.5-1.6 (1H, multiplet); 1.54 (3H, doublet, J=6.8 Hz);1.6-1.8 (4H, multiplet); 2.36-2.44 (1H, multiplet); 2.50 (2H, triplet,J=7.8 Hz); 2.59 (2H, triplet, J=7.6 Hz); 2.98-3.04 (1H, multiplet); 3.36(6H, singlet); 3.52 (4H, triplet, J=6.6 Hz); 3.45-3.55 (1H, multiplet);3.97 (2H, AB-quartet, J=16.1 Hz); 4.62 (4H, singlet); 5.16-5.23 (1H,multiplet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06 (1H,doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 10.3 Hz);7.02 (1H, singlet); 7.52 (1H, doublet of doublets, J=16.1 & 10.3 Hz)

EXAMPLE 73 14,16-Di[16-(methoxyethoxymethoxy)hexadecanoyl]radicicol

Following a procedure similar to that described in Example 12, but using400 mg of radicicol, 996 mg of 16-(methoxyethoxymethoxy)hexadecanoicacid, 6 ml of dry tetrahydrofuran, 567 mg of dicyclohexylcarbodiimideand a catalytic amount of dimethylaminopyridine, 946 mg of the titlecompound were obtained.

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1765, 1734.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.46(48H, multiplet); 1.54 (3H, doublet, J=6.4 Hz); 1.47-1.62 (1H,multiplet); 1.65-1.80 (4H, multiplet); 2.36-2.44 (1H, multiplet); 2.49(2H, triplet, J=7.3 Hz); 2.59 (2H, triplet, J=7.3 Hz); 2.98-3.04 (1H,multiplet); 3.40 (6H, singlet); 3.5-3.6 (9H, multiplet); 3.67-3.72 (4H,multiplet); 3.97 (2H, AB-quartet, J=16.1 Hz); 4.71 (4H, singlet);5.38-5.43 (1H, multiplet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9Hz); 6.06 (1H, doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets,J=10.7 & 10.3 Hz); 7.02 (1H, singlet); 7.52 (1H, doublet of doublets,J=16.1 & 10.3 Hz)

EXAMPLE 74 14,16-Di[16-(methoxymethoxy)hexadecanoyl]radicicol

Following a procedure similar to that described in Example 12, but using400 mg of radicicol, 865 mg of 10-(methoxymethoxy)decanoic acid, 7 ml ofdry tetrahydrofuran, 567 mg of dicyclohexylcarbodiimide and a catalyticamount of dimethylaminopyridine, 543 mg of the title compound wereobtained.

Infrared Absorption Spectrum (CHCl₃) ν_(max) cm⁻¹ : 1737, 1768.

Nuclear Magnetic Resonance Spectrum (CDCl₃, 270 MHz) δ ppm: 1.2-1.46(48H, multiplet); 1.54 (3H, doublet, J=6.4 Hz); 1.5-1.6 (1H, multiplet);1.6-1.77 (4H, multiplet); 2.36-2.44 (1H, multiplet); 2.50 (2H, triplet,J=7.3 Hz); 2.59 (2H, triplet, J=7.3 Hz); 2.98-3.04 (1H, multiplet); 3.36(6H, singlet); 3.52 (4H, triplet, J=6.6 Hz); 3.48-3.58 (1H, multiplet);3.97.(2H, AB-quartet, J=16.1 Hz); 4.62 (4H, singlet); 5.38-5.43 (1H,multiplet); 5.79 (1H, doublet of doublets, J=10.7 & 3.9 Hz); 6.06 (1H,doublet, J=16.1 Hz); 6.15 (1H, doublet of doublets, J=10.7 & 10.3 Hz);7.02 (1H, singlet); 7.51 (1H, doublet of doublets, J=16.6 & 10.3 Hz).

We claim:
 1. A compound of formula (I): ##STR3## wherein R¹ and R² areindependently a group R³ --CO--, in which R³ is an unsubstituted alkylgroup having 9 to 20 carbon atoms or an unsubstituted alkenyl grouphaving 9 to 20 carbon atoms.
 2. A pharmaceutical composition for thetreatment of tumors, which comprises an effective amount of an activecompound in admixture with a pharmaceutically acceptable carrier ordiluent, wherein said active compound is selected from the groupconsisting of compounds of formula (I) and salts thereof, as defined inclaim
 1. 3. A method for the treatment of tumors, which comprisesadministering to an animal an effective amount of an active compound,wherein said active compound is selected from the group consisting ofcompounds of formula (I) and salts thereof, as defined in claim 1.